11-115450414-T-C

Variant names:

• chr11-115450414-T-C
• rs314474
• NM_001301043.2:c.124+53857A>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.124+53857A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,202 control chromosomes in the GnomAD database, including 59,393 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 0.88 (59393 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.124+53857A>G		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.124+53857A>G		intron_variant	Intron 1 of 11	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133942 AN: 152084 Hom.: 59330 Cov.: 32

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.881 AC: 134063 AN: 152202 Hom.: 59393 Cov.: 32 AF XY: 0.887 AC XY: 66015 AN XY: 74410

African (AFR) AF: 0.958 AC: 39799 AN: 41536

American (AMR) AF: 0.885 AC: 13523 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2731 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5144 AN: 5170

South Asian (SAS) AF: 0.913 AC: 4409 AN: 4830

European-Finnish (FIN) AF: 0.901 AC: 9554 AN: 10602

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56173 AN: 67992

Other (OTH) AF: 0.857 AC: 1811 AN: 2112

Alfa AF: 0.843 Hom.: 27689

Bravo AF: 0.881

Asia WGS AF: 0.953 AC: 3311 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		2.4
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: rs314474; hg19: chr11-115321133;