19-6801470-G-T

Variant names:

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

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>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005428.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV1	NM_005428.4	MANE Select	c.205-19232G>T		intron	N/A	NP_005419.2
	VAV1	NM_001258206.2		c.205-19232G>T		intron	N/A	NP_001245135.1
	VAV1	NM_001258207.2		c.205-19232G>T		intron	N/A	NP_001245136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV1	ENST00000602142.6	TSL:1 MANE Select	c.205-19232G>T		intron	N/A	ENSP00000472929.1
	VAV1	ENST00000304076.6	TSL:1	c.205-19232G>T		intron	N/A	ENSP00000302269.2
	VAV1	ENST00000599806.5	TSL:1	c.39+17229G>T		intron	N/A	ENSP00000472803.1

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.54
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;