chr11-64804733-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001370259.2(MEN1):c.1434C>T(p.Gly478Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,596,958 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G478G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

MEN1
NM_001370259.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.0640

Publications

3 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 11-64804733-G-A is Benign according to our data. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806. Variant chr11-64804733-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 241806.

BP7

Synonymous conserved (PhyloP=-0.064 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000788 (12/152332) while in subpopulation EAS AF = 0.00232 (12/5180). AF 95% confidence interval is 0.00134. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEN1	NM_001370259.2 link	c.1434C>T	p.Gly478Gly	synonymous_variant	Exon 10 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.1434C>T	p.Gly478Gly	synonymous_variant	Exon 10 of 10	5	NM_001370259.2	ENSP00000394933.3		O00255-2

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00231

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:

0.000182

AC:

AN:

224684

AF XY:

0.000152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00233

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000118

AC:

171

AN:

1444626

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

718860

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33360

American (AMR)

AF:

0.00

AC:

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26018

East Asian (EAS)

AF:

0.00419

AC:

166

AN:

39640

South Asian (SAS)

AF:

0.00

AC:

AN:

86104

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5142

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110530

Other (OTH)

AF:

0.0000833

AC:

AN:

60038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000788

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00232

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000718

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Uncertain:1Benign:1

Aug 01, 2018

GeneKor MSA

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 19, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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. -

Multiple endocrine neoplasia, type 1

Benign:2

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. -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.3

(source)

DANN

Benign

0.91

PhyloP100

-0.064

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over