Genetic Variant VAMP7:c.595-10G>C (chrX-155941873-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005638.6(VAMP7):c.595-10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,610,568 control chromosomes in the GnomAD database, including 99,916 homozygotes. There are 296,583 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.33 ( 8581 hom., 26476 hem., cov: 31)

Exomes 𝑓: 0.35 ( 91335 hom. 270107 hem. )

Consequence

VAMP7
NM_005638.6 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.566

Publications

0 publications found

Variant links:

Genes affected

VAMP7 (HGNC:11486): (vesicle associated membrane protein 7) This gene encodes a transmembrane protein that is a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family. The encoded protein localizes to late endosomes and lysosomes and is involved in the fusion of transport vesicles to their target membranes. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2010]

VAMP7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant X-155941873-G-C is Benign according to our data. Variant chrX-155941873-G-C is described in ClinVar as Benign. ClinVar VariationId is 3036638.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005638.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VAMP7	NM_005638.6	MANE Select	c.595-10G>C	intron	N/A	NP_005629.1	P51809-1
VAMP7	NM_001185183.2		c.527-10G>C	intron	N/A	NP_001172112.1	P51809-2
VAMP7	NM_001145149.3		c.472-10G>C	intron	N/A	NP_001138621.1	P51809-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VAMP7	ENST00000286448.12	TSL:1 MANE Select	c.595-10G>C	intron	N/A	ENSP00000286448.6	P51809-1
VAMP7	ENST00000262640.11	TSL:1	c.527-10G>C	intron	N/A	ENSP00000262640.6	P51809-2
VAMP7	ENST00000460621.6	TSL:1	c.472-10G>C	intron	N/A	ENSP00000427822.1	P51809-3

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50610

AN:

151546

Hom.:

8573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.417

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.349

Gnomad OTH

AF:

0.328

GnomAD2 exomes

AF:

0.341

AC:

85380

AN:

250038

AF XY:

0.364

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.344

Gnomad ASJ exome

AF:

0.289

Gnomad EAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.371

Gnomad NFE exome

AF:

0.340

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.352

AC:

513554

AN:

1458904

Hom.:

91335

Cov.:

AF XY:

0.372

AC XY:

270107

AN XY:

725474

show subpopulations

African (AFR)

AF:

0.266

AC:

8872

AN:

33342

American (AMR)

AF:

0.344

AC:

15289

AN:

44462

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

7647

AN:

26014

East Asian (EAS)

AF:

0.313

AC:

12407

AN:

39652

South Asian (SAS)

AF:

0.381

AC:

32784

AN:

86070

European-Finnish (FIN)

AF:

0.354

AC:

18918

AN:

53370

Middle Eastern (MID)

AF:

0.240

AC:

1376

AN:

5744

European-Non Finnish (NFE)

AF:

0.357

AC:

395942

AN:

1109988

Other (OTH)

AF:

0.337

AC:

20319

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16330

32660

48989

65319

81649

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12736

25472

38208

50944

63680

<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:

0.334

AC:

50626

AN:

151664

Hom.:

8581

Cov.:

AF XY:

0.358

AC XY:

26476

AN XY:

74052

show subpopulations

African (AFR)

AF:

0.278

AC:

11512

AN:

41370

American (AMR)

AF:

0.344

AC:

5245

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1016

AN:

3470

East Asian (EAS)

AF:

0.328

AC:

1683

AN:

5138

South Asian (SAS)

AF:

0.401

AC:

1911

AN:

4764

European-Finnish (FIN)

AF:

0.417

AC:

4374

AN:

10500

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.349

AC:

23716

AN:

67890

Other (OTH)

AF:

0.326

AC:

685

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1708

3415

5123

6830

8538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Bravo

AF:

0.321

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

VAMP7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.65

(source)

DANN

Benign

0.57

PhyloP100

0.57

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over