11-115209591-A-ATGG

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_001301043.2(CADM1):c.1060_1061insCCA(p.Thr353dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 924,502 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (2 hom.)
• Consequence: CADM1 NM_001301043.2 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.07

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 -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001301043.2
• BP6: Variant 11-115209591-A-ATGG is Benign according to our data. Variant chr11-115209591-A-ATGG is described in ClinVar as [Likely_benign]. Clinvar id is 776659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00295 (2315/785344) while in subpopulation AFR AF= 0.0199 (400/20052). AF 95% confidence interval is 0.0183. There are 2 homozygotes in gnomad4_exome. There are 1157 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 607 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM1	NM_001301043.2	c.1060_1061insCCA	p.Thr353dup	inframe_insertion	8/12	ENST00000331581.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM1	ENST00000331581.11	c.1060_1061insCCA	p.Thr353dup	inframe_insertion	8/12	1	NM_001301043.2	P4

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 607 AN: 139034 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0246

Gnomad AMR AF: 0.00200

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00574

Gnomad SAS AF: 0.00375

Gnomad FIN AF: 0.000712

Gnomad MID AF: 0.00654

Gnomad NFE AF: 0.00105

Gnomad OTH AF: 0.00203

GnomAD3 exomes AF: 0.00270 AC: 574 AN: 212678 Hom.: 0 AF XY: 0.00252 AC XY: 291 AN XY: 115448

Gnomad AFR exome AF: 0.0119

Gnomad AMR exome AF: 0.00387

Gnomad ASJ exome AF: 0.000113

Gnomad EAS exome AF: 0.00618

Gnomad SAS exome AF: 0.00359

Gnomad FIN exome AF: 0.000263

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.000990

GnomAD4 exome AF: 0.00295 AC: 2315 AN: 785344 Hom.: 2 Cov.: 33 AF XY: 0.00283 AC XY: 1157 AN XY: 409088

Gnomad4 AFR exome AF: 0.0199

Gnomad4 AMR exome AF: 0.00358

Gnomad4 ASJ exome AF: 0.0000558

Gnomad4 EAS exome AF: 0.0110

Gnomad4 SAS exome AF: 0.00348

Gnomad4 FIN exome AF: 0.000322

Gnomad4 NFE exome AF: 0.00198

Gnomad4 OTH exome AF: 0.00453

GnomAD4 genome AF: 0.00438 AC: 610 AN: 139158 Hom.: 3 Cov.: 32 AF XY: 0.00421 AC XY: 284 AN XY: 67386

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.00200

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00574

Gnomad4 SAS AF: 0.00374

Gnomad4 FIN AF: 0.000712

Gnomad4 NFE AF: 0.00105

Gnomad4 OTH AF: 0.00201

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs747352768; hg19: chr11-115080311;