19-6822208-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005428.4(VAV1):c.450-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,566,556 control chromosomes in the GnomAD database, including 32,364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.22 ( 3752 hom., cov: 32)
Exomes 𝑓: 0.20 ( 28612 hom. )
Consequence
VAV1
NM_005428.4 splice_polypyrimidine_tract, intron
NM_005428.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.58
Genes affected
VAV1 (HGNC:12657): (vav guanine nucleotide exchange factor 1) This gene is a member of the VAV gene family. The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. The encoded protein is important in hematopoiesis, playing a role in T-cell and B-cell development and activation. The encoded protein has been identified as the specific binding partner of Nef proteins from HIV-1. Coexpression and binding of these partners initiates profound morphological changes, cytoskeletal rearrangements and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 19-6822208-T-C is Benign according to our data. Variant chr19-6822208-T-C is described in ClinVar as [Benign]. Clinvar id is 403602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VAV1 | NM_005428.4 | c.450-13T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000602142.6 | |||
VAV1 | NM_001258206.2 | c.450-13T>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
VAV1 | NM_001258207.2 | c.450-13T>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
VAV1 | XM_005259642.2 | c.450-13T>C | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VAV1 | ENST00000602142.6 | c.450-13T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005428.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.216 AC: 32839AN: 151896Hom.: 3737 Cov.: 32
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GnomAD3 exomes AF: 0.190 AC: 34138AN: 179804Hom.: 3432 AF XY: 0.188 AC XY: 17838AN XY: 94896
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GnomAD4 exome AF: 0.199 AC: 281148AN: 1414542Hom.: 28612 Cov.: 34 AF XY: 0.198 AC XY: 138135AN XY: 698928
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GnomAD4 genome AF: 0.216 AC: 32884AN: 152014Hom.: 3752 Cov.: 32 AF XY: 0.215 AC XY: 15949AN XY: 74320
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at