11-115450414-T-G

Variant names:

• chr11-115450414-T-G
• rs314474
• NM_001301043.2:c.124+53857A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001301043.2(CADM1):​c.124+53857A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CADM1 NM_001301043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301043.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	NM_001301043.2	MANE Select	c.124+53857A>C		intron	N/A	NP_001287972.1
	CADM1	NM_001301044.2		c.124+53857A>C		intron	N/A	NP_001287973.1
	CADM1	NM_001301045.2		c.124+53857A>C		intron	N/A	NP_001287974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	ENST00000331581.11	TSL:1 MANE Select	c.124+53857A>C		intron	N/A	ENSP00000329797.6
	CADM1	ENST00000537058.5	TSL:1	c.124+53857A>C		intron	N/A	ENSP00000439817.1
	CADM1	ENST00000536727.5	TSL:1	c.124+53857A>C		intron	N/A	ENSP00000440322.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		2.4

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: rs314474; hg19: chr11-115321133;