rs164022

Variant names:

• chr19-6828029-G-C
• rs164022
• NM_005428.4:c.928-47G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VAV1	NM_005428.4	c.928-47G>C		intron_variant	Intron 9 of 26	ENST00000602142.6	NP_005419.2
VAV1	NM_001258206.2	c.928-47G>C		intron_variant	Intron 9 of 25		NP_001245135.1
VAV1	NM_001258207.2	c.832-47G>C		intron_variant	Intron 8 of 25		NP_001245136.1
VAV1	XM_005259642.2	c.928-47G>C		intron_variant	Intron 9 of 25		XP_005259699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV1	ENST00000602142.6	c.928-47G>C		intron_variant	Intron 9 of 26	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

GnomAD2 exomes AF: 0.415 AC: 103319 AN: 249128 AF XY: 0.420

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 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

African (AFR) AF: 0.117 AC: 3822 AN: 32620

American (AMR) AF: 0.422 AC: 18792 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 10057 AN: 25832

East Asian (EAS) AF: 0.376 AC: 14830 AN: 39428

South Asian (SAS) AF: 0.436 AC: 37219 AN: 85430

European-Finnish (FIN) AF: 0.503 AC: 26801 AN: 53306

Middle Eastern (MID) AF: 0.318 AC: 1804 AN: 5670

European-Non Finnish (NFE) AF: 0.443 AC: 476688 AN: 1076708

Other (OTH) AF: 0.406 AC: 23961 AN: 59002

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

African (AFR) AF: 0.130 AC: 5380 AN: 41456

American (AMR) AF: 0.380 AC: 5809 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1368 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1834 AN: 5150

South Asian (SAS) AF: 0.440 AC: 2121 AN: 4816

European-Finnish (FIN) AF: 0.503 AC: 5296 AN: 10532

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29821 AN: 67948

Other (OTH) AF: 0.331 AC: 700 AN: 2112

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
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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