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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025258.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA7	NM_025258.3	MANE Select	c.2499+10C>T		intron	N/A	NP_079534.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA7	ENST00000375688.5	TSL:5 MANE Select	c.2499+10C>T		intron	N/A	ENSP00000364840.4
	VWA7	ENST00000486423.5	TSL:5	n.*164C>T		downstream_gene	N/A

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

2558

5116

7674

10232

12790

<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:

0.108

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<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:

0.0815

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 v4.9

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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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