rs7980045

Variant names:

• chr12-6095449-T-G
• rs7980045
• NM_000552.5:c.657+11A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-6095449-T-G
• chr12-6095449-T-A
• chr12-6095449-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000552.5(VWF):​c.657+11A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,613,852 control chromosomes in the GnomAD database, including 3,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1623 hom., cov: 31)
  • Exomes 𝑓: 0.039 (2280 hom.)
• Consequence: VWF NM_000552.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.11
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-6095449-T-G is Benign according to our data. Variant chr12-6095449-T-G is described in ClinVar as Benign. ClinVar VariationId is 256691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000552.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWF	NM_000552.5	MANE Select	c.657+11A>C		intron	N/A	NP_000543.3	P04275-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWF	ENST00000261405.10	TSL:1 MANE Select	c.657+11A>C		intron	N/A	ENSP00000261405.5	P04275-1
	VWF	ENST00000321023.5	TSL:1	n.*727A>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000461331.1	I3L4K4
	VWF	ENST00000321023.5	TSL:1	n.*727A>C		3_prime_UTR	Exon 7 of 7	ENSP00000461331.1	I3L4K4

Frequencies

GnomAD3 genomes AF: 0.0996 AC: 15135 AN: 151956 Hom.: 1615 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0567

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0887

GnomAD2 exomes AF: 0.0459 AC: 11540 AN: 251480 AF XY: 0.0411

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.0343

Gnomad ASJ exome AF: 0.0225

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.0346

Gnomad OTH exome AF: 0.0407

GnomAD4 exome AF: 0.0392 AC: 57340 AN: 1461778 Hom.: 2280 Cov.: 31 AF XY: 0.0386 AC XY: 28066 AN XY: 727196

African (AFR) AF: 0.277 AC: 9274 AN: 33478

American (AMR) AF: 0.0370 AC: 1655 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 556 AN: 26132

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39692

South Asian (SAS) AF: 0.0392 AC: 3377 AN: 86254

European-Finnish (FIN) AF: 0.0201 AC: 1074 AN: 53412

Middle Eastern (MID) AF: 0.0716 AC: 413 AN: 5768

European-Non Finnish (NFE) AF: 0.0341 AC: 37900 AN: 1111932

Other (OTH) AF: 0.0510 AC: 3078 AN: 60386

GnomAD4 genome AF: 0.0998 AC: 15180 AN: 152074 Hom.: 1623 Cov.: 31 AF XY: 0.0962 AC XY: 7151 AN XY: 74342

African (AFR) AF: 0.269 AC: 11158 AN: 41440

American (AMR) AF: 0.0565 AC: 864 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3468

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5148

South Asian (SAS) AF: 0.0342 AC: 165 AN: 4818

European-Finnish (FIN) AF: 0.0186 AC: 197 AN: 10614

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0364 AC: 2472 AN: 67990

Other (OTH) AF: 0.0878 AC: 185 AN: 2108

Alfa AF: 0.0609 Hom.: 1052

Bravo AF: 0.110

Asia WGS AF: 0.0400 AC: 139 AN: 3478

EpiCase AF: 0.0366

EpiControl AF: 0.0362

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hereditary von Willebrand disease (1)
-	-	1	not specified (1)
-	-	1	von Willebrand disease type 1 (1)
-	-	1	von Willebrand disease type 2 (1)
-	-	1	von Willebrand disease type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.79
DANN	Benign	0.86
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs7980045; hg19: chr12-6204615; COSMIC: COSV105047018; COSMIC: COSV105047018;