rs4445669

Variant names:

• chr11-115174517-T-C
• rs4445669
• NM_001301043.2:c.*1957A>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.*1957A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 984,800 control chromosomes in the GnomAD database, including 144,579 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 0.47 (17415 hom., cov: 30)
  • Exomes 𝑓: 0.55 (127164 hom.)
• Consequence: CADM1 NM_001301043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• Publications: 23 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=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	NM_001301043.2	MANE Select	c.*1957A>G		3_prime_UTR	Exon 12 of 12	NP_001287972.1
	CADM1	NM_001301044.2		c.*1957A>G		3_prime_UTR	Exon 11 of 11	NP_001287973.1
	CADM1	NM_001301045.2		c.*1957A>G		3_prime_UTR	Exon 11 of 11	NP_001287974.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	ENST00000331581.11	TSL:1 MANE Select	c.*1957A>G		3_prime_UTR	Exon 12 of 12	ENSP00000329797.6
	CADM1	ENST00000537058.5	TSL:1	c.*1957A>G		3_prime_UTR	Exon 11 of 11	ENSP00000439817.1
	CADM1	ENST00000536727.5	TSL:1	c.*1957A>G		3_prime_UTR	Exon 11 of 11	ENSP00000440322.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70718 AN: 151678 Hom.: 17416 Cov.: 30

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.551 AC: 458590 AN: 833004 Hom.: 127164 Cov.: 33 AF XY: 0.551 AC XY: 211806 AN XY: 384714

African (AFR) AF: 0.336 AC: 5301 AN: 15780

American (AMR) AF: 0.428 AC: 421 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 2613 AN: 5148

East Asian (EAS) AF: 0.211 AC: 764 AN: 3628

South Asian (SAS) AF: 0.416 AC: 6848 AN: 16446

European-Finnish (FIN) AF: 0.533 AC: 375 AN: 704

Middle Eastern (MID) AF: 0.451 AC: 731 AN: 1620

European-Non Finnish (NFE) AF: 0.562 AC: 427688 AN: 761412

Other (OTH) AF: 0.508 AC: 13849 AN: 27282

GnomAD4 genome AF: 0.466 AC: 70729 AN: 151796 Hom.: 17415 Cov.: 30 AF XY: 0.462 AC XY: 34287 AN XY: 74164

African (AFR) AF: 0.351 AC: 14555 AN: 41412

American (AMR) AF: 0.421 AC: 6424 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1759 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1055 AN: 5152

South Asian (SAS) AF: 0.411 AC: 1972 AN: 4800

European-Finnish (FIN) AF: 0.533 AC: 5581 AN: 10470

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37748 AN: 67922

Other (OTH) AF: 0.480 AC: 1010 AN: 2106

Alfa AF: 0.521 Hom.: 61859

Bravo AF: 0.453

Asia WGS AF: 0.287 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.24
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: rs4445669; hg19: chr11-115045237; COSMIC: COSV59012439; COSMIC: COSV59012439;