1-20336445-A-G

Position:

• chr1-20336445-A-G

Variant summary

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

The NM_001039500.3(VWA5B1):​c.1901A>G​(p.Lys634Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,483,784 control chromosomes in the GnomAD database, including 31,592 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.20 (3202 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28390 hom.)
• Consequence: VWA5B1 NM_001039500.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001645863).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA5B1	NM_001039500.3	c.1901A>G	p.Lys634Arg	missense_variant	13/22	ENST00000289815.13	NP_001034589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA5B1	ENST00000289815.13	c.1901A>G	p.Lys634Arg	missense_variant	13/22	5	NM_001039500.3	ENSP00000289815	A2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29849 AN: 152060 Hom.: 3207 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.193

GnomAD3 exomes AF: 0.223 AC: 26668 AN: 119748 Hom.: 3164 AF XY: 0.223 AC XY: 14106 AN XY: 63246

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.252

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.392

Gnomad SAS exome AF: 0.254

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.202 AC: 268735 AN: 1331606 Hom.: 28390 Cov.: 31 AF XY: 0.203 AC XY: 132162 AN XY: 652102

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.196 AC: 29850 AN: 152178 Hom.: 3202 Cov.: 32 AF XY: 0.200 AC XY: 14849 AN XY: 74410

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.196

Alfa AF: 0.188 Hom.: 6822

Bravo AF: 0.197

TwinsUK AF: 0.209 AC: 776

ALSPAC AF: 0.192 AC: 739

ESP6500AA AF: 0.171 AC: 237

ESP6500EA AF: 0.190 AC: 603

ExAC AF: 0.194 AC: 4738

Asia WGS AF: 0.311 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.2
DANN	Benign	0.87
DEOGEN2	Benign	0.0033	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.40	T;T
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.73	N;N
REVEL	Benign	0.020
Sift	Benign	0.26	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.013	B;B
Vest4		0.021
ClinPred		0.0047	T
GERP RS		-2.1
Varity_R		0.044
gMVP		0.27

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: rs10916769; hg19: chr1-20662938; COSMIC: COSV57054917;