11-115286700-C-G

Variant names:

• chr11-115286700-C-G
• rs7927241
• NM_001301043.2:c.125-46280G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000331581.11(CADM1):​c.125-46280G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,686 control chromosomes in the GnomAD database, including 11,231 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 0.35 (11231 hom., cov: 32)
• Consequence: CADM1 ENST00000331581.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000331581.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	NM_001301043.2	MANE Select	c.125-46280G>C		intron	N/A	NP_001287972.1
	CADM1	NM_001301044.2		c.125-46280G>C		intron	N/A	NP_001287973.1
	CADM1	NM_001301045.2		c.125-46280G>C		intron	N/A	NP_001287974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	ENST00000331581.11	TSL:1 MANE Select	c.125-46280G>C		intron	N/A	ENSP00000329797.6
	CADM1	ENST00000537058.5	TSL:1	c.125-46280G>C		intron	N/A	ENSP00000439817.1
	CADM1	ENST00000536727.5	TSL:1	c.125-46280G>C		intron	N/A	ENSP00000440322.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52658 AN: 151568 Hom.: 11212 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.323

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.348 AC: 52723 AN: 151686 Hom.: 11231 Cov.: 32 AF XY: 0.357 AC XY: 26471 AN XY: 74130

African (AFR) AF: 0.570 AC: 23527 AN: 41258

American (AMR) AF: 0.344 AC: 5248 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1066 AN: 3460

East Asian (EAS) AF: 0.650 AC: 3330 AN: 5122

South Asian (SAS) AF: 0.227 AC: 1096 AN: 4822

European-Finnish (FIN) AF: 0.353 AC: 3716 AN: 10524

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13773 AN: 67942

Other (OTH) AF: 0.322 AC: 678 AN: 2106

Alfa AF: 0.135 Hom.: 226

Bravo AF: 0.359

Asia WGS AF: 0.415 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7927241; hg19: chr11-115157420; COSMIC: COSV59012175;