rs220842

Variant names:

• chr11-115411454-A-T
• rs220842
• NM_001301043.2:c.124+92817T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001301043.2(CADM1):​c.124+92817T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 152,248 control chromosomes in the GnomAD database, including 71,483 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 0.97 (71483 hom., cov: 31)
• Consequence: CADM1 NM_001301043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.988 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.124+92817T>A		intron	N/A	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.124+92817T>A		intron	N/A	NP_001287973.1	X5DQR8
	CADM1	NM_001301045.2		c.124+92817T>A		intron	N/A	NP_001287974.1	X5DQS5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	ENST00000331581.11	TSL:1 MANE Select	c.124+92817T>A		intron	N/A	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.124+92817T>A		intron	N/A	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000536727.5	TSL:1	c.124+92817T>A		intron	N/A	ENSP00000440322.1	X5DQS5

Frequencies

GnomAD3 genomes AF: 0.967 AC: 147139 AN: 152130 Hom.: 71421 Cov.: 31

Gnomad AFR AF: 0.996

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.967

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.980

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

GnomAD4 genome AF: 0.967 AC: 147261 AN: 152248 Hom.: 71483 Cov.: 31 AF XY: 0.958 AC XY: 71304 AN XY: 74412

African (AFR) AF: 0.996 AC: 41410 AN: 41564

American (AMR) AF: 0.959 AC: 14666 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.967 AC: 3353 AN: 3468

East Asian (EAS) AF: 0.746 AC: 3856 AN: 5168

South Asian (SAS) AF: 0.921 AC: 4439 AN: 4820

European-Finnish (FIN) AF: 0.849 AC: 8991 AN: 10586

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.989 AC: 67295 AN: 68032

Other (OTH) AF: 0.979 AC: 2065 AN: 2110

Alfa AF: 0.981 Hom.: 9099

Bravo AF: 0.977

Asia WGS AF: 0.848 AC: 2946 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		0.39
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: rs220842; hg19: chr11-115282172;