rs11608105

Variant names:

• chr11-115380472-C-T
• rs11608105
• NM_001301043.2:c.124+123799G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001301043.2(CADM1):​c.124+123799G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 152,240 control chromosomes in the GnomAD database, including 57 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 0.025 (57 hom., cov: 32)
• Consequence: CADM1 NM_001301043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 4 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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0254 (3862/152240) while in subpopulation NFE AF = 0.0388 (2637/68008). AF 95% confidence interval is 0.0375. There are 57 homozygotes in GnomAd4. There are 1808 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3862 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.124+123799G>A		intron_variant	Intron 1 of 11	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.124+123799G>A		intron_variant	Intron 1 of 11	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3862 AN: 152122 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.00777

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0388

Gnomad OTH AF: 0.0205

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

GnomAD4 genome AF: 0.0254 AC: 3862 AN: 152240 Hom.: 57 Cov.: 32 AF XY: 0.0243 AC XY: 1808 AN XY: 74440

African (AFR) AF: 0.00775 AC: 322 AN: 41548

American (AMR) AF: 0.0243 AC: 372 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00706 AC: 34 AN: 4818

European-Finnish (FIN) AF: 0.0290 AC: 307 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0388 AC: 2637 AN: 68008

Other (OTH) AF: 0.0203 AC: 43 AN: 2116

Alfa AF: 0.0341 Hom.: 301

Bravo AF: 0.0245

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.5
DANN	Benign	0.75
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism

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: rs11608105; hg19: chr11-115251190;