Variant 11-115217927-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001301043.2(CADM1):c.786G>A(p.Ala262Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,506 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 11 hom., cov: 32)

Exomes 𝑓: 0.011 ( 127 hom. )

Consequence

CADM1
NM_001301043.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0380

Variant links:

Genes affected

CADM1 (HGNC:5951): (cell adhesion molecule 1) Enables signaling receptor binding activity. Involved in several processes, including cell recognition; positive regulation of cytokine production; and susceptibility to natural killer cell mediated cytotoxicity. Located in plasma membrane. Implicated in breast carcinoma and prostate cancer. Biomarker of cervix uteri carcinoma in situ. [provided by Alliance of Genome Resources, Apr 2022]

CADM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 11-115217927-C-T is Benign according to our data. Variant chr11-115217927-C-T is described in ClinVar as [Benign]. Clinvar id is 770982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0109 (15942/1461214) while in subpopulation MID AF= 0.0203 (117/5762). AF 95% confidence interval is 0.0173. There are 127 homozygotes in gnomad4_exome. There are 7975 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1266 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2 link	c.786G>A	p.Ala262Ala	synonymous_variant	Exon 6 of 12	ENST00000331581.11	NP_001287972.1	Q9BY67-3X5D7A8A0A4Z1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11 link	c.786G>A	p.Ala262Ala	synonymous_variant	Exon 6 of 12	1	NM_001301043.2	ENSP00000329797.6		Q9BY67-3

Frequencies

GnomAD3 genomes

AF:

0.00825

AC:

1256

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00603

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00866

AC:

2175

AN:

251204

Hom.:

AF XY:

0.00884

AC XY:

1200

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00289

Gnomad AMR exome

AF:

0.00373

Gnomad ASJ exome

AF:

0.00645

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00684

Gnomad NFE exome

AF:

0.0149

Gnomad OTH exome

AF:

0.00897

GnomAD4 exome

AF:

0.0109

AC:

15942

AN:

1461214

Hom.:

127

Cov.:

AF XY:

0.0110

AC XY:

7975

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.00404

Gnomad4 AMR exome

AF:

0.00432

Gnomad4 ASJ exome

AF:

0.00498

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00152

Gnomad4 FIN exome

AF:

0.00743

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.00923

GnomAD4 genome

AF:

0.00831

AC:

1266

AN:

152292

Hom.:

Cov.:

AF XY:

0.00794

AC XY:

591

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00342

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00603

Gnomad4 NFE

AF:

0.0140

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.00773

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0146

EpiControl

AF:

0.0148

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CADM1: BP4, BP7, BS1, BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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