rs7603439

chr2-98210693-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144992.5(VWA3B):c.1738-1237T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,146 control chromosomes in the GnomAD database, including 60,101 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 0.89 (60101 hom., cov: 30)
• Consequence: VWA3B NM_144992.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

Genes affected

VWA3B (HGNC:28385): (von Willebrand factor A domain containing 3B) This gene encodes an intracellular protein that contains a von Willebrand factor type A domain. Intracellular proteins with VWA domains are thought to function in transcription, DNA repair, ribosomal and membrane transport and the proteasome. Mutations in this gene are associated with Spinocerebellar ataxia, autosomal recessive 22. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA3B	NM_144992.5	c.1738-1237T>G		intron_variant		ENST00000477737.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA3B	ENST00000477737.6	c.1738-1237T>G		intron_variant		1	NM_144992.5	P1

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134860 AN: 152028 Hom.: 60046 Cov.: 30

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.858

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.887 AC: 134974 AN: 152146 Hom.: 60101 Cov.: 30 AF XY: 0.891 AC XY: 66294 AN XY: 74376

Gnomad4 AFR AF: 0.944

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.956

Gnomad4 FIN AF: 0.918

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.860

Alfa AF: 0.858 Hom.: 25813

Bravo AF: 0.885

Asia WGS AF: 0.953 AC: 3315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.1
Dann	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs7603439; hg19: chr2-98827156;