Genetic Variant VWA5B1:p.Ser156Ser (chr1-20314497-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001039500.3(VWA5B1):c.468C>T(p.Ser156Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000902 in 1,551,766 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

VWA5B1
NM_001039500.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.326

Publications

0 publications found

Variant links:

Genes affected

VWA5B1 (HGNC:26538): (von Willebrand factor A domain containing 5B1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

VWA5B1 links:

ENSG00000226664 (HGNC:41146):

ENSG00000226664 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP7

Synonymous conserved (PhyloP=-0.326 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039500.3. 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
	VWA5B1	NM_001039500.3	MANE Select	c.468C>T	p.Ser156Ser	synonymous	Exon 4 of 22	NP_001034589.2	Q5TIE3-2
	VWA5B1	NM_001377531.1		c.153C>T	p.Ser51Ser	synonymous	Exon 4 of 22	NP_001364460.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VWA5B1	ENST00000289815.13	TSL:5 MANE Select	c.468C>T	p.Ser156Ser	synonymous	Exon 4 of 22	ENSP00000289815.9	Q5TIE3-2
VWA5B1	ENST00000919186.1		c.468C>T	p.Ser156Ser	synonymous	Exon 4 of 22	ENSP00000589245.1
VWA5B1	ENST00000375079.6	TSL:5	c.468C>T	p.Ser156Ser	synonymous	Exon 4 of 22	ENSP00000364220.1	Q5TIE3-1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000230

AC:

AN:

156722

AF XY:

0.000229

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000810

Gnomad ASJ exome

AF:

0.00282

Gnomad EAS exome

AF:

0.000275

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000825

Gnomad OTH exome

AF:

0.000454

GnomAD4 exome

AF:

0.0000893

AC:

125

AN:

1399472

Hom.:

Cov.:

AF XY:

0.0000797

AC XY:

AN XY:

690256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.0000840

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00266

AC:

AN:

25182

East Asian (EAS)

AF:

0.000140

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000334

AC:

AN:

1078986

Other (OTH)

AF:

0.000241

AC:

AN:

58028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000985

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41562

American (AMR)

AF:

0.000131

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000291

Hom.:

Bravo

AF:

0.000102

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_noAF

Benign

-0.27

CADD

Benign

9.4

(source)

DANN

Benign

0.94

PhyloP100

-0.33

Mutation Taster

=99/1

polymorphism

(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