dbSNP rs12638540: CMTM7:c.334-2412A>G (chr3-32447042-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.262

Publications

16 publications found

Variant links:

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]

CMTM7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 124 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMTM7	NM_138410.4 link	c.334-2412A>G		intron_variant	Intron 2 of 4	ENST00000334983.10	NP_612419.1	Q96FZ5-1
CMTM7	NM_181472.3 link	c.333+5029A>G		intron_variant	Intron 2 of 3		NP_852137.1	Q96FZ5-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CMTM7	ENST00000334983.10 link	c.334-2412A>G	intron_variant	Intron 2 of 4	1	NM_138410.4	ENSP00000335605.5	Q96FZ5-1
CMTM7	ENST00000349718.8 link	c.333+5029A>G	intron_variant	Intron 2 of 3	1		ENSP00000283621.5	Q96FZ5-2
CMTM7	ENST00000465248.1 link	c.201+5029A>G	intron_variant	Intron 2 of 2	2		ENSP00000440333.1	H0YFU6
CMTM7	ENST00000454304.6 link	n.334-2412A>G	intron_variant	Intron 2 of 4	5		ENSP00000414480.2	F8WDZ3

Frequencies

GnomAD3 genomes

AF:

0.0324

AC:

4925

AN:

152106

Hom.:

126

Cov.:

show subpopulations

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.:

AF XY:

0.0352

AC XY:

2617

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00821

AC:

341

AN:

41552

American (AMR)

AF:

0.0283

AC:

432

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0574

AC:

199

AN:

3468

East Asian (EAS)

AF:

0.0549

AC:

285

AN:

5188

South Asian (SAS)

AF:

0.0487

AC:

235

AN:

4822

European-Finnish (FIN)

AF:

0.0811

AC:

858

AN:

10576

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0356

AC:

2421

AN:

68012

Other (OTH)

AF:

0.0360

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

241

482

723

964

1205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0349

Hom.:

300

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

(source)

DANN

Benign

0.92

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over