rs61736636

Positions:

chr11-64809675-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001370259.2(MEN1):c.435C>T(p.Ser145=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0354 in 1,614,046 control chromosomes in the GnomAD database, including 1,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 89 hom., cov: 31)

Exomes 𝑓: 0.036 ( 1151 hom. )

Consequence

MEN1
NM_001370259.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:17

Conservation

PhyloP100: 3.77

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 11-64809675-G-A is Benign according to our data. Variant chr11-64809675-G-A is described in ClinVar as [Benign]. Clinvar id is 96252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64809675-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0267 (4070/152278) while in subpopulation NFE AF= 0.0407 (2768/68018). AF 95% confidence interval is 0.0394. There are 89 homozygotes in gnomad4. There are 2015 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4070 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEN1	NM_001370259.2 linkuse as main transcript	c.435C>T	p.Ser145=	synonymous_variant	2/10	ENST00000450708.7	NP_001357188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEN1	ENST00000450708.7 linkuse as main transcript	c.435C>T	p.Ser145=	synonymous_variant	2/10	5	NM_001370259.2	ENSP00000394933	P3	O00255-2

Frequencies

GnomAD3 genomes

AF:

0.0267

AC:

4070

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00760

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.0655

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0407

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0278

AC:

6989

AN:

251364

Hom.:

161

AF XY:

0.0281

AC XY:

3818

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00671

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.00794

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00764

Gnomad FIN exome

AF:

0.0644

Gnomad NFE exome

AF:

0.0406

Gnomad OTH exome

AF:

0.0315

GnomAD4 exome

AF:

0.0363

AC:

53020

AN:

1461768

Hom.:

1151

Cov.:

AF XY:

0.0356

AC XY:

25866

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00603

Gnomad4 AMR exome

AF:

0.00982

Gnomad4 ASJ exome

AF:

0.00716

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00765

Gnomad4 FIN exome

AF:

0.0634

Gnomad4 NFE exome

AF:

0.0417

Gnomad4 OTH exome

AF:

0.0286

GnomAD4 genome

AF:

0.0267

AC:

4070

AN:

152278

Hom.:

Cov.:

AF XY:

0.0271

AC XY:

2015

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00758

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00704

Gnomad4 FIN

AF:

0.0655

Gnomad4 NFE

AF:

0.0407

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.0333

Hom.:

Bravo

AF:

0.0213

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0339

EpiControl

AF:

0.0334

ClinVar

Significance: Benign

Submissions summary: Benign:17

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 30, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 01, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	May 18, 2022	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Multiple endocrine neoplasia, type 1

Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Mar 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

Hereditary cancer-predisposing syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	May 22, 2015	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. -
Benign, criteria provided, single submitter	curation	Sema4, Sema4	Jul 08, 2020	- -

Hyperparathyroidism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over