rs878855188

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001370259.2(MEN1):c.1230C>T(p.Phe410Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

MEN1
NM_001370259.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.211

Publications

0 publications found

Variant links:

Genes affected

MEN1 (HGNC:7010): (menin 1) This gene encodes menin, a tumor suppressor associated with a syndrome known as multiple endocrine neoplasia type 1. Menin is a scaffold protein that functions in histone modification and epigenetic gene regulation. It is thought to regulate several pathways and processes by altering chromatin structure through the modification of histones. [provided by RefSeq, May 2019]

MEN1 Gene-Disease associations (from GenCC):

multiple endocrine neoplasia type 1
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Ambry Genetics
familial isolated hyperparathyroidism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
pituitary gigantism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

MEN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 11-64805154-G-A is Benign according to our data. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64805154-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 241799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.211 with no splicing effect.

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEN1	NM_001370259.2 link	c.1230C>T	p.Phe410Phe	synonymous_variant	Exon 9 of 10	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7 link	c.1230C>T	p.Phe410Phe	synonymous_variant	Exon 9 of 10	5	NM_001370259.2	ENSP00000394933.3		O00255-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

251032

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461734

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000447

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.000704

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1111994

Other (OTH)

AF:

0.0000166

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000120

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Multiple endocrine neoplasia, type 1

Benign:3

Dec 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 05, 2024

Myriad Genetics, Inc.

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -

Hereditary cancer-predisposing syndrome

Benign:1

Sep 01, 2016

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over