1-1435945-C-CCGGGCGGGGGCG

Position:

• chr1-1435945-C-CCGGGCGGGGGCG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_022834.5(VWA1):​c.73+132_73+143dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 562,696 control chromosomes in the GnomAD database, including 5,554 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (5220 hom., cov: 28)
  • Exomes 𝑓: 0.0071 (334 hom.)
• Consequence: VWA1 NM_022834.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54

Genes affected

VWA1 (HGNC:30910): (von Willebrand factor A domain containing 1) VWA1 belongs to the von Willebrand factor (VWF; MIM 613160) A (VWFA) domain superfamily of extracellular matrix proteins and appears to play a role in cartilage structure and function (Fitzgerald et al., 2002 [PubMed 12062410]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-1435945-C-CCGGGCGGGGGCG is Benign according to our data. Variant chr1-1435945-C-CCGGGCGGGGGCG is described in ClinVar as [Benign]. Clinvar id is 1264926.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VWA1	NM_022834.5	c.73+132_73+143dup		intron_variant		ENST00000476993.2	NP_073745.2
VWA1	NM_199121.3	c.73+132_73+143dup		intron_variant			NP_954572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VWA1	ENST00000476993.2	c.73+132_73+143dup		intron_variant		1	NM_022834.5	ENSP00000417185	P1
VWA1	ENST00000338660.5	c.73+132_73+143dup		intron_variant		2		ENSP00000423404
VWA1	ENST00000471398.1	c.73+132_73+143dup		intron_variant		3		ENSP00000464343
VWA1	ENST00000495558.1	c.-33+807_-33+818dup		intron_variant		2		ENSP00000463643

Frequencies

GnomAD3 genomes AF: 0.218 AC: 32906 AN: 150680 Hom.: 5203 Cov.: 28

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.00713 AC: 2935 AN: 411912 Hom.: 334 AF XY: 0.00748 AC XY: 1462 AN XY: 195450

Gnomad4 AFR exome AF: 0.00776

Gnomad4 AMR exome AF: 0.0241

Gnomad4 ASJ exome AF: 0.00484

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.00664

Gnomad4 NFE exome AF: 0.00543

Gnomad4 OTH exome AF: 0.0102

GnomAD4 genome AF: 0.219 AC: 32955 AN: 150784 Hom.: 5220 Cov.: 28 AF XY: 0.232 AC XY: 17060 AN XY: 73586

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.222

Alfa AF: 0.0647 Hom.: 57

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553196206; hg19: chr1-1371325;