Variant chr11-115229275-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001301043.2(CADM1):c.563-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,613,914 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 50 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 32 hom. )

Consequence

CADM1
NM_001301043.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003252

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.373

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-115229275-G-A is Benign according to our data. Variant chr11-115229275-G-A is described in ClinVar as [Benign]. Clinvar id is 776661.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1913/152260) while in subpopulation AFR AF= 0.0435 (1808/41546). AF 95% confidence interval is 0.0418. There are 50 homozygotes in gnomad4. There are 907 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1913 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM1	NM_001301043.2 linkuse as main transcript	c.563-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		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.563-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001301043.2	ENSP00000329797	P4	Q9BY67-3

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1908

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00338

AC:

848

AN:

251178

Hom.:

AF XY:

0.00246

AC XY:

334

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.0448

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00143

AC:

2093

AN:

1461654

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

916

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0463

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000188

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.0126

AC:

1913

AN:

152260

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

907

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0435

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00646

Hom.:

Bravo

AF:

0.0147

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.86

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.0

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