11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGG

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BS1 BS2

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. 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

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001301043.2
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0154 (7054/457382) while in subpopulation EAS AF= 0.0202 (266/13176). AF 95% confidence interval is 0.0182. There are 0 homozygotes in gnomad4_exome. There are 3659 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 7054 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.1058_1060delCCA	p.Thr353del	disruptive_inframe_deletion	Exon 8 of 12	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.1058_1060delCCA	p.Thr353del	disruptive_inframe_deletion	Exon 8 of 12	1	NM_001301043.2	ENSP00000329797.6

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

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

Gnomad4 AFR exome AF: 0.0119

Gnomad4 AMR exome AF: 0.0121

Gnomad4 ASJ exome AF: 0.0147

Gnomad4 EAS exome AF: 0.0202

Gnomad4 SAS exome AF: 0.0131

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0147

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

Gnomad4 AFR AF: 0.000207

Gnomad4 AMR AF: 0.0000714

Gnomad4 ASJ AF: 0.000305

Gnomad4 EAS AF: 0.00275

Gnomad4 SAS AF: 0.000267

Gnomad4 FIN AF: 0.000119

Gnomad4 NFE AF: 0.000172

Gnomad4 OTH AF: 0.00101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs747352768; hg19: chr11-115080311;