11-115298909-A-G

Variant names:

• chr11-115298909-A-G
• rs11215474
• NM_001301043.2:c.125-58489T>C

Variant summary

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

The NM_001301043.2(CADM1):​c.125-58489T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,812 control chromosomes in the GnomAD database, including 11,318 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 0.35 (11318 hom., cov: 32)
• Consequence: CADM1 NM_001301043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 1 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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.125-58489T>C		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.125-58489T>C		intron_variant	Intron 1 of 11	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52980 AN: 151692 Hom.: 11303 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.349 AC: 53042 AN: 151812 Hom.: 11318 Cov.: 32 AF XY: 0.359 AC XY: 26619 AN XY: 74190

African (AFR) AF: 0.565 AC: 23351 AN: 41348

American (AMR) AF: 0.352 AC: 5366 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3462

East Asian (EAS) AF: 0.652 AC: 3345 AN: 5132

South Asian (SAS) AF: 0.203 AC: 974 AN: 4808

European-Finnish (FIN) AF: 0.356 AC: 3751 AN: 10542

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14189 AN: 67960

Other (OTH) AF: 0.328 AC: 690 AN: 2104

Alfa AF: 0.290 Hom.: 955

Bravo AF: 0.360

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.52
PhyloP100		0.13
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: rs11215474; hg19: chr11-115169629;