Genetic Variant CMTM7:c.432+40T>C (chr3-32449592-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

Publications

7 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=-0.9).

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 rank	MANE	Protein	UniProt
CMTM7	NM_138410.4 link	c.432+40T>C		intron_variant	Intron 3 of 4	ENST00000334983.10	NP_612419.1	Q96FZ5-1
CMTM7	NM_181472.3 link	c.334-2800T>C		intron_variant	Intron 2 of 3		NP_852137.1	Q96FZ5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMTM7	ENST00000334983.10 link	c.432+40T>C		intron_variant	Intron 3 of 4	1	NM_138410.4	ENSP00000335605.5		Q96FZ5-1

Frequencies

GnomAD3 genomes

AF:

0.0583

AC:

8867

AN:

152138

Hom.:

289

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0644

AC XY:

42405

AN XY:

658284

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4131

8262

12393

16524

20655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2274

4548

6822

9096

11370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0582

AC:

8865

AN:

152256

Hom.:

289

Cov.:

AF XY:

0.0601

AC XY:

4475

AN XY:

74428

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0651

AC:

4430

AN:

68010

Other (OTH)

AF:

0.0662

AC:

140

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

429

857

1286

1714

2143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0632

Hom.:

593

Bravo

AF:

0.0563

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.55

(source)

DANN

Benign

0.43

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over