rs2617815

chr19-6795136-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005428.4(VAV1):c.204+22125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,982 control chromosomes in the GnomAD database, including 3,925 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 0.22 (3925 hom., cov: 31)
• Consequence: VAV1 NM_005428.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.07

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV1	NM_005428.4	c.204+22125A>G		intron_variant		ENST00000602142.6
VAV1	NM_001258206.2	c.204+22125A>G		intron_variant
VAV1	NM_001258207.2	c.204+22125A>G		intron_variant
VAV1	XM_005259642.2	c.204+22125A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV1	ENST00000602142.6	c.204+22125A>G		intron_variant		1	NM_005428.4	P1
VAV1	ENST00000304076.6	c.204+22125A>G		intron_variant		1
VAV1	ENST00000599806.5	c.39+10895A>G		intron_variant		1
VAV1	ENST00000596764.5	c.204+22125A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33493 AN: 151862 Hom.: 3923 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33519 AN: 151982 Hom.: 3925 Cov.: 31 AF XY: 0.218 AC XY: 16186 AN XY: 74284

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.224

Alfa AF: 0.210 Hom.: 2043

Bravo AF: 0.225

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.1
Dann	Benign	0.31

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: rs2617815; hg19: chr19-6795147;