19-6801470-G-C

Variant names:

• chr19-6801470-G-C
• rs2617822
• NM_005428.4:c.205-19232G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005428.4(VAV1):​c.205-19232G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,846 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 29)
• Consequence: VAV1 NM_005428.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 13 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV1	NM_005428.4	c.205-19232G>C		intron_variant	Intron 1 of 26	ENST00000602142.6	NP_005419.2
VAV1	NM_001258206.2	c.205-19232G>C		intron_variant	Intron 1 of 25		NP_001245135.1
VAV1	NM_001258207.2	c.205-19232G>C		intron_variant	Intron 1 of 25		NP_001245136.1
VAV1	XM_005259642.2	c.205-19232G>C		intron_variant	Intron 1 of 25		XP_005259699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV1	ENST00000602142.6	c.205-19232G>C		intron_variant	Intron 1 of 26	1	NM_005428.4	ENSP00000472929.1
VAV1	ENST00000304076.6	c.205-19232G>C		intron_variant	Intron 1 of 25	1		ENSP00000302269.2
VAV1	ENST00000599806.5	c.39+17229G>C		intron_variant	Intron 1 of 26	1		ENSP00000472803.1
VAV1	ENST00000596764.5	c.205-19232G>C		intron_variant	Intron 1 of 25	2		ENSP00000469450.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151846 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151846 Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1 AN XY: 74142

African (AFR) AF: 0.0000484 AC: 2 AN: 41296

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 176560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.42
PhyloP100		-0.57

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: rs2617822; hg19: chr19-6801481;