chr11-115172854-T-G

Variant names:

• chr11-115172854-T-G
• rs17564430
• NM_001301043.2:c.*3620A>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.*3620A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 150,404 control chromosomes in the GnomAD database, including 3,612 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 0.20 (3609 hom., cov: 28)
  • Exomes 𝑓: 0.23 (3 hom.)
• Consequence: CADM1 NM_001301043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 11 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.*3620A>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.*3620A>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30475 AN: 150226 Hom.: 3604 Cov.: 28

Gnomad AFR AF: 0.0875

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.227 AC: 15 AN: 66 Hom.: 3 Cov.: 0 AF XY: 0.229 AC XY: 11 AN XY: 48

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 13 AN: 52

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.203 AC: 30487 AN: 150338 Hom.: 3609 Cov.: 28 AF XY: 0.206 AC XY: 15092 AN XY: 73306

African (AFR) AF: 0.0874 AC: 3570 AN: 40854

American (AMR) AF: 0.289 AC: 4331 AN: 14988

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 577 AN: 3464

East Asian (EAS) AF: 0.143 AC: 727 AN: 5076

South Asian (SAS) AF: 0.322 AC: 1519 AN: 4724

European-Finnish (FIN) AF: 0.274 AC: 2808 AN: 10240

Middle Eastern (MID) AF: 0.233 AC: 67 AN: 288

European-Non Finnish (NFE) AF: 0.242 AC: 16421 AN: 67720

Other (OTH) AF: 0.193 AC: 401 AN: 2074

Alfa AF: 0.222 Hom.: 10979

Bravo AF: 0.195

Asia WGS AF: 0.227 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.40
PhyloP100		0.11
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: rs17564430; hg19: chr11-115043574;