rs164022

Positions:

• chr19-6828029-G-C

Variant summary

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

The NM_005428.4(VAV1):​c.928-47G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,574,472 control chromosomes in the GnomAD database, including 145,767 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 0.35 (10703 hom., cov: 31)
  • Exomes 𝑓: 0.43 (135064 hom.)
• Consequence: VAV1 NM_005428.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV1	NM_005428.4	c.928-47G>C		intron_variant		ENST00000602142.6	NP_005419.2
VAV1	NM_001258206.2	c.928-47G>C		intron_variant			NP_001245135.1
VAV1	NM_001258207.2	c.832-47G>C		intron_variant			NP_001245136.1
VAV1	XM_005259642.2	c.928-47G>C		intron_variant			XP_005259699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV1	ENST00000602142.6	c.928-47G>C		intron_variant		1	NM_005428.4	ENSP00000472929.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52860 AN: 151850 Hom.: 10708 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.333

GnomAD3 exomes AF: 0.415 AC: 103319 AN: 249128 Hom.: 22286 AF XY: 0.420 AC XY: 56520 AN XY: 134702

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.429

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.369

Gnomad SAS exome AF: 0.436

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.440

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.432 AC: 613974 AN: 1422506 Hom.: 135064 Cov.: 23 AF XY: 0.432 AC XY: 306322 AN XY: 709862

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.376

Gnomad4 SAS exome AF: 0.436

Gnomad4 FIN exome AF: 0.503

Gnomad4 NFE exome AF: 0.443

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.348 AC: 52850 AN: 151966 Hom.: 10703 Cov.: 31 AF XY: 0.354 AC XY: 26268 AN XY: 74244

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.331

Alfa AF: 0.396 Hom.: 2388

Bravo AF: 0.327

Asia WGS AF: 0.359 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.30

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: rs164022; hg19: chr19-6828040; COSMIC: COSV58387508; COSMIC: COSV58387508;