chr19-6795136-A-G

Variant names:

• chr19-6795136-A-G
• rs2617815
• NM_005428.4:c.204+22125A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005428.4(VAV1):​c.204+22125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,982 control chromosomes in the GnomAD database, including 3,925 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 0.22 (3925 hom., cov: 31)
• Consequence: VAV1 NM_005428.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.07
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV1	NM_005428.4	MANE Select	c.204+22125A>G		intron	N/A	NP_005419.2
	VAV1	NM_001258206.2		c.204+22125A>G		intron	N/A	NP_001245135.1
	VAV1	NM_001258207.2		c.204+22125A>G		intron	N/A	NP_001245136.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV1	ENST00000602142.6	TSL:1 MANE Select	c.204+22125A>G		intron	N/A	ENSP00000472929.1
	VAV1	ENST00000304076.6	TSL:1	c.204+22125A>G		intron	N/A	ENSP00000302269.2
	VAV1	ENST00000599806.5	TSL:1	c.39+10895A>G		intron	N/A	ENSP00000472803.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33493 AN: 151862 Hom.: 3923 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.221 AC: 33519 AN: 151982 Hom.: 3925 Cov.: 31 AF XY: 0.218 AC XY: 16186 AN XY: 74284

African (AFR) AF: 0.299 AC: 12379 AN: 41432

American (AMR) AF: 0.170 AC: 2589 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3470

East Asian (EAS) AF: 0.140 AC: 722 AN: 5168

South Asian (SAS) AF: 0.214 AC: 1029 AN: 4812

European-Finnish (FIN) AF: 0.164 AC: 1737 AN: 10576

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13663 AN: 67970

Other (OTH) AF: 0.224 AC: 472 AN: 2104

Alfa AF: 0.211 Hom.: 2276

Bravo AF: 0.225

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.31
PhyloP100		-3.1
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: rs2617815; hg19: chr19-6795147;