rs4936894

Positions:

• chr11-124146786-G-A

Variant summary

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

The NM_001130142.2(VWA5A):​c.*841G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,364 control chromosomes in the GnomAD database, including 3,265 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 0.19 (3256 hom., cov: 31)
  • Exomes 𝑓: 0.24 (9 hom.)
• Consequence: VWA5A NM_001130142.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54

Genes affected

VWA5A (HGNC:6658): (von Willebrand factor A domain containing 5A) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VWA5A	NM_001130142.2	c.*841G>A		3_prime_UTR_variant	19/19	ENST00000456829.7
VWA5A	NM_014622.5	c.*841G>A		3_prime_UTR_variant	18/18
VWA5A	XM_011542828.3	c.*841G>A		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VWA5A	ENST00000456829.7	c.*841G>A		3_prime_UTR_variant	19/19	1	NM_001130142.2	P1
VWA5A	ENST00000392748.5	c.*841G>A		3_prime_UTR_variant	18/18	1		P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28502 AN: 151922 Hom.: 3260 Cov.: 31

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.238 AC: 77 AN: 324 Hom.: 9 Cov.: 0 AF XY: 0.235 AC XY: 38 AN XY: 162

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.188 AC: 28508 AN: 152040 Hom.: 3256 Cov.: 31 AF XY: 0.191 AC XY: 14194 AN XY: 74308

Gnomad4 AFR AF: 0.0707

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.188

Alfa AF: 0.217 Hom.: 8115

Bravo AF: 0.186

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.046
DANN	Benign	0.47

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: rs4936894; hg19: chr11-124017493;