chr12-6023913-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000552.5(VWF):​c.3223-126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 1,010,306 control chromosomes in the GnomAD database, including 4,098 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.089 ( 617 hom., cov: 32)
Exomes 𝑓: 0.085 ( 3481 hom. )

Consequence

VWF
NM_000552.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.90
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VWFNM_000552.5 linkuse as main transcriptc.3223-126A>G intron_variant ENST00000261405.10
VWFXM_047429501.1 linkuse as main transcriptc.3223-126A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VWFENST00000261405.10 linkuse as main transcriptc.3223-126A>G intron_variant 1 NM_000552.5 P1P04275-1
VWFENST00000538635.5 linkuse as main transcriptn.421-29979A>G intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.0889
AC:
13537
AN:
152192
Hom.:
618
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.106
Gnomad AMI
AF:
0.0735
Gnomad AMR
AF:
0.0656
Gnomad ASJ
AF:
0.0504
Gnomad EAS
AF:
0.122
Gnomad SAS
AF:
0.154
Gnomad FIN
AF:
0.0753
Gnomad MID
AF:
0.0633
Gnomad NFE
AF:
0.0807
Gnomad OTH
AF:
0.0935
GnomAD4 exome
AF:
0.0853
AC:
73204
AN:
857996
Hom.:
3481
AF XY:
0.0884
AC XY:
39082
AN XY:
442222
show subpopulations
Gnomad4 AFR exome
AF:
0.108
Gnomad4 AMR exome
AF:
0.0506
Gnomad4 ASJ exome
AF:
0.0500
Gnomad4 EAS exome
AF:
0.110
Gnomad4 SAS exome
AF:
0.152
Gnomad4 FIN exome
AF:
0.0751
Gnomad4 NFE exome
AF:
0.0797
Gnomad4 OTH exome
AF:
0.0848
GnomAD4 genome
AF:
0.0889
AC:
13540
AN:
152310
Hom.:
617
Cov.:
32
AF XY:
0.0901
AC XY:
6708
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.106
Gnomad4 AMR
AF:
0.0655
Gnomad4 ASJ
AF:
0.0504
Gnomad4 EAS
AF:
0.121
Gnomad4 SAS
AF:
0.154
Gnomad4 FIN
AF:
0.0753
Gnomad4 NFE
AF:
0.0807
Gnomad4 OTH
AF:
0.0930
Alfa
AF:
0.0788
Hom.:
70
Bravo
AF:
0.0875
Asia WGS
AF:
0.116
AC:
406
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.026
DANN
Benign
0.83

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2854871; hg19: chr12-6133079; API