rs4445669

Positions:

• chr11-115174517-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001301043.2(CADM1):​c.*1957A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 984,800 control chromosomes in the GnomAD database, including 144,579 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (17415 hom., cov: 30)
  • Exomes 𝑓: 0.55 (127164 hom.)
• Consequence: CADM1 NM_001301043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.*1957A>G		3_prime_UTR_variant	12/12	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.*1957A>G		3_prime_UTR_variant	12/12	1	NM_001301043.2	ENSP00000329797	P4

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70718 AN: 151678 Hom.: 17416 Cov.: 30

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.551 AC: 458590 AN: 833004 Hom.: 127164 Cov.: 33 AF XY: 0.551 AC XY: 211806 AN XY: 384714

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.533

Gnomad4 NFE exome AF: 0.562

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.466 AC: 70729 AN: 151796 Hom.: 17415 Cov.: 30 AF XY: 0.462 AC XY: 34287 AN XY: 74164

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.480

Alfa AF: 0.528 Hom.: 37265

Bravo AF: 0.453

Asia WGS AF: 0.287 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.83

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: rs4445669; hg19: chr11-115045237; COSMIC: COSV59012439; COSMIC: COSV59012439;