chr11-115249895-C-T

Variant names:

• chr11-115249895-C-T
• rs10502199
• NM_001301043.2:c.125-9475G>A

Variant summary

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

The NM_001301043.2(CADM1):​c.125-9475G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0956 in 152,208 control chromosomes in the GnomAD database, including 966 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 0.096 (966 hom., cov: 32)
• Consequence: CADM1 NM_001301043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.125-9475G>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.125-9475G>A		intron_variant	Intron 1 of 11	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14551 AN: 152090 Hom.: 967 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.0948

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.0976

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

GnomAD4 genome AF: 0.0956 AC: 14551 AN: 152208 Hom.: 966 Cov.: 32 AF XY: 0.0912 AC XY: 6787 AN XY: 74404

African (AFR) AF: 0.0255 AC: 1061 AN: 41556

American (AMR) AF: 0.0947 AC: 1448 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0270 AC: 130 AN: 4822

European-Finnish (FIN) AF: 0.0763 AC: 808 AN: 10586

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10021 AN: 67990

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.136 Hom.: 1261

Bravo AF: 0.0969

Asia WGS AF: 0.0150 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.71
PhyloP100		-0.82
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: rs10502199; hg19: chr11-115120615;