rs12638540

chr3-32447042-A-Gchr3-32447042-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_138410.4(CMTM7):c.334-2412A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 152,224 control chromosomes in the GnomAD database, including 124 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 0.032 (124 hom., cov: 32)
• Consequence: CMTM7 NM_138410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262

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=-0.76).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0323 (4919/152224) while in subpopulation EAS AF= 0.0549 (285/5188). AF 95% confidence interval is 0.0497. There are 124 homozygotes in gnomad4. There are 2617 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 126 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMTM7	NM_138410.4	c.334-2412A>G		intron_variant		ENST00000334983.10
CMTM7	NM_181472.3	c.333+5029A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMTM7	ENST00000334983.10	c.334-2412A>G		intron_variant		1	NM_138410.4	P1
CMTM7	ENST00000349718.8	c.333+5029A>G		intron_variant		1
CMTM7	ENST00000465248.1	c.201+5029A>G		intron_variant		2
CMTM7	ENST00000454304.6	c.334-2412A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4925 AN: 152106 Hom.: 126 Cov.: 32

Gnomad AFR AF: 0.00818

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.0574

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0356

Gnomad OTH AF: 0.0364

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0323 AC: 4919 AN: 152224 Hom.: 124 Cov.: 32 AF XY: 0.0352 AC XY: 2617 AN XY: 74420

Gnomad4 AFR AF: 0.00821

Gnomad4 AMR AF: 0.0283

Gnomad4 ASJ AF: 0.0574

Gnomad4 EAS AF: 0.0549

Gnomad4 SAS AF: 0.0487

Gnomad4 FIN AF: 0.0811

Gnomad4 NFE AF: 0.0356

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0358 Hom.: 169

Bravo AF: 0.0275

Asia WGS AF: 0.0370 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	4.4
Dann	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12638540; hg19: chr3-32488534;