Genetic Variant NM_025258.3:c.2499+10C>T (chr6-31765873-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_025258.3(VWA7):c.2499+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 1,612,670 control chromosomes in the GnomAD database, including 5,274 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 0.11 ( 1221 hom., cov: 32)

Exomes 𝑓: 0.068 ( 4053 hom. )

Consequence

VWA7
NM_025258.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

31 publications found

Variant links:

Genes affected

VWA7 (HGNC:13939): (von Willebrand factor A domain containing 7) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

VWA7 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 (REVEL=0.008).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA7	NM_025258.3 link	c.2499+10C>T		intron_variant	Intron 16 of 16	ENST00000375688.5	NP_079534.2	Q9Y334-1A0A1U9X8T7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWA7	ENST00000375688.5 link	c.2499+10C>T		intron_variant	Intron 16 of 16	5	NM_025258.3	ENSP00000364840.4		Q9Y334-1
VWA7	ENST00000486423.5 link	n.*164C>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16477

AN:

152148

Hom.:

1222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.0485

Gnomad AMR

AF:

0.0700

Gnomad ASJ

AF:

0.0524

Gnomad EAS

AF:

0.0749

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0703

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0696

Gnomad OTH

AF:

0.107

GnomAD2 exomes

AF:

0.0802

AC:

19665

AN:

245104

AF XY:

0.0800

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.0528

Gnomad ASJ exome

AF:

0.0557

Gnomad EAS exome

AF:

0.0930

Gnomad FIN exome

AF:

0.0701

Gnomad NFE exome

AF:

0.0679

Gnomad OTH exome

AF:

0.0735

GnomAD4 exome

AF:

0.0677

AC:

98797

AN:

1460404

Hom.:

4053

Cov.:

AF XY:

0.0682

AC XY:

49556

AN XY:

726428

show subpopulations

African (AFR)

AF:

0.216

AC:

7232

AN:

33470

American (AMR)

AF:

0.0562

AC:

2515

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0546

AC:

1426

AN:

26114

East Asian (EAS)

AF:

0.0449

AC:

1783

AN:

39690

South Asian (SAS)

AF:

0.105

AC:

9025

AN:

86250

European-Finnish (FIN)

AF:

0.0689

AC:

3603

AN:

52292

Middle Eastern (MID)

AF:

0.0778

AC:

449

AN:

5768

European-Non Finnish (NFE)

AF:

0.0616

AC:

68487

AN:

1111740

Other (OTH)

AF:

0.0708

AC:

4277

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

5676

11352

17029

22705

28381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.108

AC:

16478

AN:

152266

Hom.:

1221

Cov.:

AF XY:

0.108

AC XY:

8018

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.205

AC:

8499

AN:

41526

American (AMR)

AF:

0.0697

AC:

1067

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0524

AC:

182

AN:

3472

East Asian (EAS)

AF:

0.0755

AC:

391

AN:

5182

South Asian (SAS)

AF:

0.116

AC:

561

AN:

4830

European-Finnish (FIN)

AF:

0.0703

AC:

747

AN:

10624

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0696

AC:

4732

AN:

68018

Other (OTH)

AF:

0.106

AC:

223

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

752

1504

2256

3008

3760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0815

Hom.:

2430

Bravo

AF:

0.113

Asia WGS

AF:

0.0850

AC:

293

AN:

3478

EpiCase

AF:

0.0694

EpiControl

AF:

0.0713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.35

(source)

DANN

Benign

0.75

PhyloP100

-1.0

Mutation Taster

=99/1

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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NM_025258.3:c.2499+10C>T

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