Variant 11-115209645-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001301043.2(CADM1):c.1007C>T(p.Thr336Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,612,888 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 5 hom. )

Consequence

CADM1
NM_001301043.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.37

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007242739).

BP6

Variant 11-115209645-G-A is Benign according to our data. Variant chr11-115209645-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 782217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 339 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM1	NM_001301043.2 linkuse as main transcript	c.1007C>T	p.Thr336Ile	missense_variant	8/12	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11 linkuse as main transcript	c.1007C>T	p.Thr336Ile	missense_variant	8/12	1	NM_001301043.2	ENSP00000329797	P4	Q9BY67-3

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

339

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000871

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000625

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00315

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00226

AC:

556

AN:

246048

Hom.:

AF XY:

0.00225

AC XY:

300

AN XY:

133154

show subpopulations

Gnomad AFR exome

AF:

0.000685

Gnomad AMR exome

AF:

0.00383

Gnomad ASJ exome

AF:

0.00492

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00106

Gnomad FIN exome

AF:

0.0000955

Gnomad NFE exome

AF:

0.00284

Gnomad OTH exome

AF:

0.00281

GnomAD4 exome

AF:

0.00290

AC:

4242

AN:

1460924

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

2058

AN XY:

726640

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00429

Gnomad4 ASJ exome

AF:

0.00490

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.00327

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00223

AC:

339

AN:

151964

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.000869

Gnomad4 AMR

AF:

0.00426

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000625

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00315

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00270

Hom.:

Bravo

AF:

0.00277

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00188

AC:

228

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 20, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Benign

0.88

DEOGEN2

Benign

0.13

T;.;.;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.0073

MetaRNN

Benign

0.0072

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.8

N;N;N;.

REVEL

Benign

0.11

Sift

Benign

0.18

T;T;T;.

Sift4G

Benign

0.086

T;T;T;T

Polyphen

0.017

B;.;.;.

Vest4

0.73

MVP

0.35

MPC

0.71

ClinPred

0.028

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.50

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