1-20336445-A-G

Variant names:

• chr1-20336445-A-G
• rs10916769
• NM_001039500.3:c.1901A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA5B1	NM_001039500.3	MANE Select	c.1901A>G	p.Lys634Arg	missense	Exon 13 of 22	NP_001034589.2
	VWA5B1	NM_001377531.1		c.1586A>G	p.Lys529Arg	missense	Exon 13 of 22	NP_001364460.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWA5B1	ENST00000289815.13	TSL:5 MANE Select	c.1901A>G	p.Lys634Arg	missense	Exon 13 of 22	ENSP00000289815.9
	VWA5B1	ENST00000525343.1	TSL:1	n.177A>G		non_coding_transcript_exon	Exon 2 of 10
	VWA5B1	ENST00000375079.6	TSL:5	c.1901A>G	p.Lys634Arg	missense	Exon 13 of 22	ENSP00000364220.1

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

GnomAD2 exomes AF: 0.223 AC: 26668 AN: 119748 AF XY: 0.223

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 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

African (AFR) AF: 0.156 AC: 4588 AN: 29504

American (AMR) AF: 0.229 AC: 6368 AN: 27760

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4437 AN: 23294

East Asian (EAS) AF: 0.394 AC: 13049 AN: 33160

South Asian (SAS) AF: 0.244 AC: 16045 AN: 65886

European-Finnish (FIN) AF: 0.203 AC: 9828 AN: 48308

Middle Eastern (MID) AF: 0.148 AC: 808 AN: 5468

European-Non Finnish (NFE) AF: 0.194 AC: 202002 AN: 1043084

Other (OTH) AF: 0.211 AC: 11610 AN: 55142

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

African (AFR) AF: 0.160 AC: 6644 AN: 41534

American (AMR) AF: 0.219 AC: 3350 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 696 AN: 3466

East Asian (EAS) AF: 0.393 AC: 2032 AN: 5170

South Asian (SAS) AF: 0.249 AC: 1202 AN: 4822

European-Finnish (FIN) AF: 0.212 AC: 2244 AN: 10592

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.190 AC: 12883 AN: 67982

Other (OTH) AF: 0.196 AC: 413 AN: 2112

Alfa AF: 0.188 Hom.: 10094

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 v4.9

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
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.11
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.020
Sift	Benign	0.26	T
Sift4G	Benign	0.43	T
Polyphen		0.013	B
Vest4		0.021
ClinPred		0.0047	T
GERP RS		-2.1
Varity_R		0.044
gMVP		0.27
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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