11-115233452-T-C

Variant names:

• chr11-115233452-T-C
• rs11215437
• NM_001301043.2:c.425-1962A>G

Variant summary

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

The NM_001301043.2(CADM1):​c.425-1962A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,088 control chromosomes in the GnomAD database, including 7,616 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 0.30 (7616 hom., cov: 32)
• Consequence: CADM1 NM_001301043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.425-1962A>G		intron_variant	Intron 3 of 11	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.425-1962A>G		intron_variant	Intron 3 of 11	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45744 AN: 151970 Hom.: 7604 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.301 AC: 45797 AN: 152088 Hom.: 7616 Cov.: 32 AF XY: 0.305 AC XY: 22682 AN XY: 74348

African (AFR) AF: 0.355 AC: 14736 AN: 41458

American (AMR) AF: 0.311 AC: 4753 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3468

East Asian (EAS) AF: 0.648 AC: 3354 AN: 5174

South Asian (SAS) AF: 0.468 AC: 2255 AN: 4822

European-Finnish (FIN) AF: 0.200 AC: 2121 AN: 10594

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16642 AN: 67974

Other (OTH) AF: 0.320 AC: 677 AN: 2114

Alfa AF: 0.265 Hom.: 11133

Bravo AF: 0.305

Asia WGS AF: 0.564 AC: 1955 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.78
PhyloP100		0.66
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: rs11215437; hg19: chr11-115104172;