chr12-6110516-G-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_000552.5(VWF):c.390C>T(p.Ser130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00932 in 1,614,116 control chromosomes in the GnomAD database, including 917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 84 hom., cov: 32)
Exomes 𝑓: 0.0088 ( 833 hom. )
Consequence
VWF
NM_000552.5 synonymous
NM_000552.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.67
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 12-6110516-G-A is Benign according to our data. Variant chr12-6110516-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 256676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6110516-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.67 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VWF | NM_000552.5 | c.390C>T | p.Ser130= | synonymous_variant | 5/52 | ENST00000261405.10 | |
VWF | XM_047429501.1 | c.390C>T | p.Ser130= | synonymous_variant | 5/52 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VWF | ENST00000261405.10 | c.390C>T | p.Ser130= | synonymous_variant | 5/52 | 1 | NM_000552.5 | P1 | |
VWF | ENST00000321023.5 | c.*449C>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/7 | 1 | ||||
VWF | ENST00000538635.5 | n.419C>T | splice_region_variant, non_coding_transcript_exon_variant | 5/6 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0143 AC: 2173AN: 152106Hom.: 85 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
2173
AN:
152106
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0174 AC: 4379AN: 251490Hom.: 269 AF XY: 0.0160 AC XY: 2173AN XY: 135920
GnomAD3 exomes
AF:
AC:
4379
AN:
251490
Hom.:
AF XY:
AC XY:
2173
AN XY:
135920
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00880 AC: 12864AN: 1461892Hom.: 833 Cov.: 31 AF XY: 0.00875 AC XY: 6363AN XY: 727246
GnomAD4 exome
AF:
AC:
12864
AN:
1461892
Hom.:
Cov.:
31
AF XY:
AC XY:
6363
AN XY:
727246
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0143 AC: 2177AN: 152224Hom.: 84 Cov.: 32 AF XY: 0.0147 AC XY: 1093AN XY: 74424
GnomAD4 genome
?
AF:
AC:
2177
AN:
152224
Hom.:
Cov.:
32
AF XY:
AC XY:
1093
AN XY:
74424
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
171
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 03, 2022 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
von Willebrand disease type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
von Willebrand disease type 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
von Willebrand disease type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Hereditary von Willebrand disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at