11-115226236-A-T

Variant names:

• chr11-115226236-A-T
• rs6589488
• NM_001301043.2:c.721+2877T>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.721+2877T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 152,274 control chromosomes in the GnomAD database, including 62,657 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 0.91 (62657 hom., cov: 33)
• Consequence: CADM1 NM_001301043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.721+2877T>A		intron_variant	Intron 5 of 11	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.721+2877T>A		intron_variant	Intron 5 of 11	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.905 AC: 137732 AN: 152156 Hom.: 62600 Cov.: 33

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.905 AC: 137849 AN: 152274 Hom.: 62657 Cov.: 33 AF XY: 0.910 AC XY: 67757 AN XY: 74450

African (AFR) AF: 0.975 AC: 40518 AN: 41556

American (AMR) AF: 0.899 AC: 13741 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2930 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5186

South Asian (SAS) AF: 0.973 AC: 4702 AN: 4830

European-Finnish (FIN) AF: 0.931 AC: 9883 AN: 10610

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58105 AN: 68016

Other (OTH) AF: 0.900 AC: 1905 AN: 2116

Alfa AF: 0.880 Hom.: 7329

Bravo AF: 0.903

Asia WGS AF: 0.983 AC: 3416 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.75
PhyloP100		-0.47
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: rs6589488; hg19: chr11-115096956;