3-32449592-T-C

Position:

• chr3-32449592-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000334983.10(CMTM7):​c.432+40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 1,458,442 control chromosomes in the GnomAD database, including 3,275 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 0.058 (289 hom., cov: 32)
  • Exomes 𝑓: 0.065 (2986 hom.)
• Consequence: CMTM7 ENST00000334983.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

Genes affected

CMTM7 (HGNC:19178): (CKLF like MARVEL transmembrane domain containing 7) This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and transmembrane 4 superfamilies. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 3. This gene acts as a tumor suppressor that regulates G1/S transition in the cell cycle, and epidermal growth factor receptor/protein kinase B signaling during tumor pathogenesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM7	NM_138410.4	c.432+40T>C		intron_variant		ENST00000334983.10	NP_612419.1
CMTM7	NM_181472.3	c.334-2800T>C		intron_variant			NP_852137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTM7	ENST00000334983.10	c.432+40T>C		intron_variant		1	NM_138410.4	ENSP00000335605	P1

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8867 AN: 152138 Hom.: 289 Cov.: 32

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0651

Gnomad OTH AF: 0.0669

GnomAD3 exomes AF: 0.0584 AC: 14675 AN: 251142 Hom.: 488 AF XY: 0.0602 AC XY: 8171 AN XY: 135782

Gnomad AFR exome AF: 0.0341

Gnomad AMR exome AF: 0.0368

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.0621

Gnomad SAS exome AF: 0.0445

Gnomad FIN exome AF: 0.0760

Gnomad NFE exome AF: 0.0631

Gnomad OTH exome AF: 0.0741

GnomAD4 exome AF: 0.0648 AC: 84697 AN: 1306186 Hom.: 2986 Cov.: 19 AF XY: 0.0644 AC XY: 42405 AN XY: 658284

Gnomad4 AFR exome AF: 0.0374

Gnomad4 AMR exome AF: 0.0388

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.0884

Gnomad4 SAS exome AF: 0.0475

Gnomad4 FIN exome AF: 0.0757

Gnomad4 NFE exome AF: 0.0652

Gnomad4 OTH exome AF: 0.0693

GnomAD4 genome AF: 0.0582 AC: 8865 AN: 152256 Hom.: 289 Cov.: 32 AF XY: 0.0601 AC XY: 4475 AN XY: 74428

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.0521

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0703

Gnomad4 SAS AF: 0.0499

Gnomad4 FIN AF: 0.0765

Gnomad4 NFE AF: 0.0651

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0638 Hom.: 465

Bravo AF: 0.0563

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.43

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: rs2304593; hg19: chr3-32491084; COSMIC: COSV58551654; COSMIC: COSV58551654;