11-115209591-ATGGTGGTGG-A

Position:

• chr11-115209591-ATGGTGGTGG-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS2

The NM_001301043.2(CADM1):​c.1052_1060del​(p.Thr351_Thr353del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000772 in 924,982 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (1 hom.)
• Consequence: CADM1 NM_001301043.2 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.96

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 -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001301043.2
• BP6: Variant 11-115209591-ATGGTGGTGG-A is Benign according to our data. Variant chr11-115209591-ATGGTGGTGG-A is described in ClinVar as [Benign]. Clinvar id is 733505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 78 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.1052_1060del	p.Thr351_Thr353del	inframe_deletion	8/12	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.1052_1060del	p.Thr351_Thr353del	inframe_deletion	8/12	1	NM_001301043.2	ENSP00000329797	P4

Frequencies

GnomAD3 genomes AF: 0.000547 AC: 76 AN: 139038 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000715

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.00107

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000626

Gnomad OTH AF: 0.000509

GnomAD3 exomes AF: 0.00122 AC: 259 AN: 212678 Hom.: 1 AF XY: 0.00123 AC XY: 142 AN XY: 115448

Gnomad AFR exome AF: 0.000219

Gnomad AMR exome AF: 0.0000349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0141

Gnomad SAS exome AF: 0.00120

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000165

Gnomad OTH exome AF: 0.000198

GnomAD4 exome AF: 0.000809 AC: 636 AN: 785820 Hom.: 1 AF XY: 0.000845 AC XY: 346 AN XY: 409302

Gnomad4 AFR exome AF: 0.000349

Gnomad4 AMR exome AF: 0.000100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0136

Gnomad4 SAS exome AF: 0.00134

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000269

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.000560 AC: 78 AN: 139162 Hom.: 0 Cov.: 32 AF XY: 0.000742 AC XY: 50 AN XY: 67384

Gnomad4 AFR AF: 0.000310

Gnomad4 AMR AF: 0.0000714

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.00107

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000626

Gnomad4 OTH AF: 0.00151

Bravo AF: 0.000695

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	Jul 01, 2024	CADM1: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 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;