11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGG

Variant names:

• chr11-115209591-ATGG-A
• rs747352768
• NM_001301043.2:c.1058_1060delCCA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001301043.2(CADM1):​c.1058_1060delCCA​(p.Thr353del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 457,382 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CADM1 NM_001301043.2 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53
• 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001301043.2

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.1058_1060delCCA	p.Thr353del	disruptive_inframe_deletion	Exon 8 of 12	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.1058_1060delCCA	p.Thr353del	disruptive_inframe_deletion	Exon 8 of 11	NP_001287973.1	X5DQR8
	CADM1	NM_014333.4		c.1058_1060delCCA	p.Thr353del	disruptive_inframe_deletion	Exon 8 of 10	NP_055148.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	ENST00000331581.11	TSL:1 MANE Select	c.1058_1060delCCA	p.Thr353del	disruptive_inframe_deletion	Exon 8 of 12	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.1058_1060delCCA	p.Thr353del	disruptive_inframe_deletion	Exon 8 of 11	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000452722.7	TSL:1	c.1058_1060delCCA	p.Thr353del	disruptive_inframe_deletion	Exon 8 of 10	ENSP00000395359.2	Q9BY67-1

Frequencies

GnomAD3 genomes AF: 0.000259 AC: 36 AN: 138954 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000207

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000716

Gnomad ASJ AF: 0.000305

Gnomad EAS AF: 0.00275

Gnomad SAS AF: 0.000268

Gnomad FIN AF: 0.000119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000172

Gnomad OTH AF: 0.00102

GnomAD2 exomes AF: 0.0120 AC: 2548 AN: 212678 AF XY: 0.0127

Gnomad AFR exome AF: 0.00780

Gnomad AMR exome AF: 0.0116

Gnomad ASJ exome AF: 0.0114

Gnomad EAS exome AF: 0.0130

Gnomad FIN exome AF: 0.0180

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.0101

GnomAD4 exome AF: 0.0154 AC: 7054 AN: 457382 Hom.: 0 AF XY: 0.0149 AC XY: 3659 AN XY: 245830

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0119 AC: 148 AN: 12386

American (AMR) AF: 0.0121 AC: 388 AN: 32128

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 167 AN: 11394

East Asian (EAS) AF: 0.0202 AC: 266 AN: 13176

South Asian (SAS) AF: 0.0131 AC: 700 AN: 53350

European-Finnish (FIN) AF: 0.0172 AC: 499 AN: 28942

Middle Eastern (MID) AF: 0.00833 AC: 24 AN: 2880

European-Non Finnish (NFE) AF: 0.0161 AC: 4582 AN: 284130

Other (OTH) AF: 0.0147 AC: 280 AN: 18996

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000259 AC: 36 AN: 139076 Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 19 AN XY: 67326

African (AFR) AF: 0.000207 AC: 8 AN: 38718

American (AMR) AF: 0.0000714 AC: 1 AN: 13996

Ashkenazi Jewish (ASJ) AF: 0.000305 AC: 1 AN: 3274

East Asian (EAS) AF: 0.00275 AC: 11 AN: 4004

South Asian (SAS) AF: 0.000267 AC: 1 AN: 3740

European-Finnish (FIN) AF: 0.000119 AC: 1 AN: 8390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000172 AC: 11 AN: 63830

Other (OTH) AF: 0.00101 AC: 2 AN: 1988

Alfa AF: 0.0224 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747352768; hg19: chr11-115080311; COSMIC: COSV59002377; COSMIC: COSV59002377;