11-115209322-C-G

Variant names:

• chr11-115209322-C-G
• rs7125361
• NM_001301043.2:c.1078+252G>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.1078+252G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,026 control chromosomes in the GnomAD database, including 16,174 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 0.46 (16174 hom., cov: 32)
• Consequence: CADM1 NM_001301043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

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.1078+252G>C		intron	N/A	NP_001287972.1
	CADM1	NM_001301044.2		c.1078+252G>C		intron	N/A	NP_001287973.1
	CADM1	NM_001301045.2		c.994+5286G>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.1078+252G>C		intron	N/A	ENSP00000329797.6
	CADM1	ENST00000537058.5	TSL:1	c.1078+252G>C		intron	N/A	ENSP00000439817.1
	CADM1	ENST00000536727.5	TSL:1	c.994+5286G>C		intron	N/A	ENSP00000440322.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69539 AN: 151908 Hom.: 16143 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.458 AC: 69624 AN: 152026 Hom.: 16174 Cov.: 32 AF XY: 0.460 AC XY: 34176 AN XY: 74316

African (AFR) AF: 0.495 AC: 20528 AN: 41440

American (AMR) AF: 0.526 AC: 8039 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3470

East Asian (EAS) AF: 0.516 AC: 2658 AN: 5154

South Asian (SAS) AF: 0.454 AC: 2190 AN: 4820

European-Finnish (FIN) AF: 0.456 AC: 4817 AN: 10568

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28444 AN: 67972

Other (OTH) AF: 0.448 AC: 946 AN: 2112

Alfa AF: 0.431 Hom.: 1744

Bravo AF: 0.465

Asia WGS AF: 0.524 AC: 1822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.8
DANN	Benign	0.54
PhyloP100		0.66
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: rs7125361; hg19: chr11-115080042;