11-115209591-ATGGTGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGGTGGTGG

Variant names:

• chr11-115209591-A-ATGGTGG
• rs747352768
• NM_001301043.2:c.1055_1060dupCCACCA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001301043.2(CADM1):​c.1055_1060dupCCACCA​(p.Thr352_Thr353dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 924,976 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: CADM1 NM_001301043.2 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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 Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001301043.2
• BS2: High AC in GnomAd4 at 178 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.1055_1060dupCCACCA	p.Thr352_Thr353dup	conservative_inframe_insertion	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.1055_1060dupCCACCA	p.Thr352_Thr353dup	conservative_inframe_insertion	Exon 8 of 12	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 179 AN: 139034 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00432

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000286

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000536

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000626

Gnomad OTH AF: 0.00102

GnomAD3 exomes AF: 0.000296 AC: 63 AN: 212678 Hom.: 0 AF XY: 0.000225 AC XY: 26 AN XY: 115448

Gnomad AFR exome AF: 0.00350

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000204

Gnomad SAS exome AF: 0.000231

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000620

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000321 AC: 252 AN: 785818 Hom.: 1 Cov.: 33 AF XY: 0.000298 AC XY: 122 AN XY: 409300

Gnomad4 AFR exome AF: 0.00817

Gnomad4 AMR exome AF: 0.000150

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000783

Gnomad4 SAS exome AF: 0.000207

Gnomad4 FIN exome AF: 0.0000248

Gnomad4 NFE exome AF: 0.000102

Gnomad4 OTH exome AF: 0.000294

GnomAD4 genome AF: 0.00128 AC: 178 AN: 139158 Hom.: 0 Cov.: 32 AF XY: 0.00131 AC XY: 88 AN XY: 67384

Gnomad4 AFR AF: 0.00431

Gnomad4 AMR AF: 0.000286

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000267

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000626

Gnomad4 OTH AF: 0.00101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;