11-115230847-C-T

Variant names:

• chr11-115230847-C-T
• rs10790068
• NM_001301043.2:c.562+506G>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.562+506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,192 control chromosomes in the GnomAD database, including 47,343 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 0.78 (47343 hom., cov: 33)
• Consequence: CADM1 NM_001301043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.562+506G>A		intron_variant	Intron 4 of 11	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.562+506G>A		intron_variant	Intron 4 of 11	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119071 AN: 152074 Hom.: 47290 Cov.: 33

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.783 AC: 119184 AN: 152192 Hom.: 47343 Cov.: 33 AF XY: 0.781 AC XY: 58142 AN XY: 74402

African (AFR) AF: 0.789 AC: 32762 AN: 41520

American (AMR) AF: 0.826 AC: 12646 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2485 AN: 3472

East Asian (EAS) AF: 0.317 AC: 1638 AN: 5168

South Asian (SAS) AF: 0.762 AC: 3672 AN: 4820

European-Finnish (FIN) AF: 0.825 AC: 8741 AN: 10592

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54859 AN: 68006

Other (OTH) AF: 0.773 AC: 1632 AN: 2110

Alfa AF: 0.777 Hom.: 4835

Bravo AF: 0.779

Asia WGS AF: 0.589 AC: 2048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.036
DANN	Benign	0.66
PhyloP100		-2.2
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: rs10790068; hg19: chr11-115101567;