rs2617822

Positions:

• chr19-6801470-G-A
• chr19-6801470-G-C
• chr19-6801470-G-T

Variant summary

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

The NM_005428.4(VAV1):​c.205-19232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 151,900 control chromosomes in the GnomAD database, including 43,180 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 0.73 (43180 hom., cov: 29)
• Consequence: VAV1 NM_005428.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV1	NM_005428.4	c.205-19232G>A		intron_variant		ENST00000602142.6	NP_005419.2
VAV1	NM_001258206.2	c.205-19232G>A		intron_variant			NP_001245135.1
VAV1	NM_001258207.2	c.205-19232G>A		intron_variant			NP_001245136.1
VAV1	XM_005259642.2	c.205-19232G>A		intron_variant			XP_005259699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV1	ENST00000602142.6	c.205-19232G>A		intron_variant		1	NM_005428.4	ENSP00000472929	P1
VAV1	ENST00000304076.6	c.205-19232G>A		intron_variant		1		ENSP00000302269
VAV1	ENST00000599806.5	c.39+17229G>A		intron_variant		1		ENSP00000472803
VAV1	ENST00000596764.5	c.205-19232G>A		intron_variant		2		ENSP00000469450

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111008 AN: 151782 Hom.: 43187 Cov.: 29

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.731 AC: 111020 AN: 151900 Hom.: 43180 Cov.: 29 AF XY: 0.740 AC XY: 54915 AN XY: 74238

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.937

Gnomad4 SAS AF: 0.887

Gnomad4 FIN AF: 0.911

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.740

Alfa AF: 0.818 Hom.: 90204

Bravo AF: 0.709

Asia WGS AF: 0.841 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.55

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: rs2617822; hg19: chr19-6801481;