3-32449592-T-C

Variant names:

• chr3-32449592-T-C
• rs2304593
• NM_138410.4:c.432+40T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138410.4(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 NM_138410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138410.4. 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
	CMTM7	NM_138410.4	MANE Select	c.432+40T>C		intron	N/A	NP_612419.1	Q96FZ5-1
	CMTM7	NM_181472.3		c.334-2800T>C		intron	N/A	NP_852137.1	Q96FZ5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTM7	ENST00000334983.10	TSL:1 MANE Select	c.432+40T>C		intron	N/A	ENSP00000335605.5	Q96FZ5-1
	CMTM7	ENST00000349718.8	TSL:1	c.334-2800T>C		intron	N/A	ENSP00000283621.5	Q96FZ5-2
	CMTM7	ENST00000875110.1		c.432+40T>C		intron	N/A	ENSP00000545169.1

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

GnomAD2 exomes AF: 0.0584 AC: 14675 AN: 251142 AF XY: 0.0602

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 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

African (AFR) AF: 0.0374 AC: 1124 AN: 30068

American (AMR) AF: 0.0388 AC: 1729 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 2718 AN: 25188

East Asian (EAS) AF: 0.0884 AC: 3451 AN: 39024

South Asian (SAS) AF: 0.0475 AC: 3947 AN: 83140

European-Finnish (FIN) AF: 0.0757 AC: 4040 AN: 53358

Middle Eastern (MID) AF: 0.109 AC: 595 AN: 5458

European-Non Finnish (NFE) AF: 0.0652 AC: 63262 AN: 970142

Other (OTH) AF: 0.0693 AC: 3831 AN: 55258

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

African (AFR) AF: 0.0354 AC: 1469 AN: 41554

American (AMR) AF: 0.0521 AC: 796 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3470

East Asian (EAS) AF: 0.0703 AC: 364 AN: 5176

South Asian (SAS) AF: 0.0499 AC: 241 AN: 4828

European-Finnish (FIN) AF: 0.0765 AC: 812 AN: 10608

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0651 AC: 4430 AN: 68010

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

Alfa AF: 0.0632 Hom.: 593

Bravo AF: 0.0563

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.43
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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