11-115217927-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001301043.2(CADM1):c.786G>A(p.Ala262=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0380

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]

ACMG classification

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 GnomAd at 1256 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM1	NM_001301043.2	c.786G>A	p.Ala262=	synonymous_variant	6/12	ENST00000331581.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM1	ENST00000331581.11	c.786G>A	p.Ala262=	synonymous_variant	6/12	1	NM_001301043.2	P4

Frequencies

GnomAD3 genomes AF: 0.00825 AC: 1256 AN: 152174 Hom.: 10 Cov.: 32

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.: 21 AF XY: 0.00884 AC XY: 1200 AN XY: 135768

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.: 30 AF XY: 0.0110 AC XY: 7975 AN XY: 726944

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.: 11 Cov.: 32 AF XY: 0.00794 AC XY: 591 AN XY: 74462

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.: 6

Bravo AF: 0.00773

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0146

EpiControl AF: 0.0148

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	CADM1: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	11
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

Other links and lift over

dbSNP: rs113893105; hg19: chr11-115088647; COSMIC: COSV100523695; COSMIC: COSV100523695;