Genetic Variant VWA1:c.73+132_73+143dupGGGCGCGGGCGG (chr1-1435945-C-CCGGGCGGGGGCG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_022834.5(VWA1):c.73+132_73+143dupGGGCGCGGGCGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 562,696 control chromosomes in the GnomAD database, including 5,554 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 5220 hom., cov: 28)

Exomes 𝑓: 0.0071 ( 334 hom. )

Consequence

VWA1
NM_022834.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.54

Variant links:

Genes affected

VWA1 (HGNC:30910): (von Willebrand factor A domain containing 1) VWA1 belongs to the von Willebrand factor (VWF; MIM 613160) A (VWFA) domain superfamily of extracellular matrix proteins and appears to play a role in cartilage structure and function (Fitzgerald et al., 2002 [PubMed 12062410]).[supplied by OMIM, Nov 2010]

VWA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-1435945-C-CCGGGCGGGGGCG is Benign according to our data. Variant chr1-1435945-C-CCGGGCGGGGGCG is described in ClinVar as [Benign]. Clinvar id is 1264926.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWA1	NM_022834.5 link	c.73+132_73+143dupGGGCGCGGGCGG		intron_variant	Intron 1 of 2	ENST00000476993.2	NP_073745.2	Q6PCB0-1
VWA1	NM_199121.3 link	c.73+132_73+143dupGGGCGCGGGCGG		intron_variant	Intron 1 of 2		NP_954572.2	Q6PCB0-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
VWA1	ENST00000476993.2 link	c.73+124_73+125insCGGGCGGGGGCG	intron_variant	Intron 1 of 2	1	NM_022834.5	ENSP00000417185.1	Q6PCB0-1
VWA1	ENST00000495558.1 link	c.-33+799_-33+800insCGGGCGGGGGCG	intron_variant	Intron 1 of 1	2		ENSP00000463643.1	J3QLP3
VWA1	ENST00000471398.1 link	c.73+124_73+125insCGGGCGGGGGCG	intron_variant	Intron 1 of 1	3		ENSP00000464343.1	J3QRR0
VWA1	ENST00000338660.5 link	c.73+124_73+125insCGGGCGGGGGCG	intron_variant	Intron 1 of 2	2		ENSP00000423404.1	Q6PCB0-3

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

32906

AN:

150680

Hom.:

5203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.846

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.00713

AC:

2935

AN:

411912

Hom.:

334

AF XY:

0.00748

AC XY:

1462

AN XY:

195450

show subpopulations

Gnomad4 AFR exome

AF:

0.00776

AC:

AN:

6830

Gnomad4 AMR exome

AF:

0.0241

AC:

AN:

956

Gnomad4 ASJ exome

AF:

0.00484

AC:

AN:

3722

Gnomad4 EAS exome

AF:

0.290

AC:

AN:

290

Gnomad4 SAS exome

AF:

0.133

AC:

539

AN:

4058

Gnomad4 FIN exome

AF:

0.00664

AC:

AN:

3766

Gnomad4 NFE exome

AF:

0.00543

AC:

2056

AN:

378338

Gnomad4 Remaining exome

AF:

0.0102

AC:

133

AN:

13054

Heterozygous variant carriers

109

218

327

436

545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.219

AC:

32955

AN:

150784

Hom.:

5220

Cov.:

AF XY:

0.232

AC XY:

17060

AN XY:

73586

show subpopulations

Gnomad4 AFR

AF:

0.211

AC:

0.210538

AN:

0.210538

Gnomad4 AMR

AF:

0.332

AC:

0.332191

AN:

0.332191

Gnomad4 ASJ

AF:

0.121

AC:

0.120949

AN:

0.120949

Gnomad4 EAS

AF:

0.846

AC:

0.845934

AN:

0.845934

Gnomad4 SAS

AF:

0.506

AC:

0.505848

AN:

0.505848

Gnomad4 FIN

AF:

0.200

AC:

0.199961

AN:

0.199961

Gnomad4 NFE

AF:

0.141

AC:

0.141454

AN:

0.141454

Gnomad4 OTH

AF:

0.222

AC:

0.22164

AN:

0.22164

Heterozygous variant carriers

1080

2159

3239

4318

5398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.0647

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 17, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over