12-6095736-CA-C

Variant names:

• chr12-6095736-CA-C
• rs5796209
• NM_000552.5:c.533-153delT

Variant summary

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

The NM_000552.5(VWF):​c.533-153delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (24261 hom., cov: 0)
  • Exomes 𝑓: 0.64 (188566 hom.)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347

Genes affected

VWF (HGNC:12726): (von Willebrand factor) This gene encodes a glycoprotein involved in hemostasis. The encoded preproprotein is proteolytically processed following assembly into large multimeric complexes. These complexes function in the adhesion of platelets to sites of vascular injury and the transport of various proteins in the blood. Mutations in this gene result in von Willebrand disease, an inherited bleeding disorder. An unprocessed pseudogene has been found on chromosome 22. [provided by RefSeq, Oct 2015]

RN7SL69P (HGNC:46085): (RNA, 7SL, cytoplasmic 69, pseudogene)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-6095736-CA-C is Benign according to our data. Variant chr12-6095736-CA-C is described in ClinVar as [Benign]. Clinvar id is 1291468.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VWF	NM_000552.5	c.533-153delT		intron_variant	Intron 5 of 51	ENST00000261405.10	NP_000543.3
VWF	XM_047429501.1	c.533-153delT		intron_variant	Intron 5 of 51		XP_047285457.1
RN7SL69P		n.6095737delA		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VWF	ENST00000261405.10	c.533-153delT		intron_variant	Intron 5 of 51	1	NM_000552.5	ENSP00000261405.5
VWF	ENST00000321023.5	n.*592-153delT		intron_variant	Intron 6 of 6	1		ENSP00000461331.1
RN7SL69P	ENST00000468423.3	n.234delT		non_coding_transcript_exon_variant	Exon 1 of 1	6
VWF	ENST00000538635.5	n.420+14778delT		intron_variant	Intron 5 of 5	4

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82045 AN: 151792 Hom.: 24272 Cov.: 0

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.639 AC: 577081 AN: 903558 Hom.: 188566 Cov.: 0 AF XY: 0.645 AC XY: 301116 AN XY: 467196

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.521

Gnomad4 ASJ exome AF: 0.707

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.712

Gnomad4 FIN exome AF: 0.603

Gnomad4 NFE exome AF: 0.645

Gnomad4 OTH exome AF: 0.637

GnomAD4 genome AF: 0.540 AC: 82047 AN: 151910 Hom.: 24261 Cov.: 0 AF XY: 0.545 AC XY: 40442 AN XY: 74244

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.730

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.577

Alfa AF: 0.346 Hom.: 755

Bravo AF: 0.525

Asia WGS AF: 0.653 AC: 2271 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs5796209; hg19: chr12-6204902;