1-107574039-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006113.5(VAV3):c.2502+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,613,466 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (57 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (86 hom.)
• Consequence: VAV3 NM_006113.5 splice_region, intron
• Scores: Splicing: ADA: 0.00007108
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.719

Genes affected

VAV3 (HGNC:12659): (vav guanine nucleotide exchange factor 3) 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. This gene product acts as a GEF preferentially for RhoG, RhoA, and to a lesser extent, RAC1, and it associates maximally with the nucleotide-free states of these GTPases. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-107574039-C-T is Benign according to our data. Variant chr1-107574039-C-T is described in ClinVar as [Benign]. Clinvar id is 717806.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV3	NM_006113.5	c.2502+8G>A		splice_region_variant, intron_variant		ENST00000370056.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV3	ENST00000370056.9	c.2502+8G>A		splice_region_variant, intron_variant		1	NM_006113.5	P1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2505 AN: 152112 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00949

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00910

GnomAD3 exomes AF: 0.00658 AC: 1650 AN: 250700 Hom.: 38 AF XY: 0.00601 AC XY: 814 AN XY: 135488

Gnomad AFR exome AF: 0.0560

Gnomad AMR exome AF: 0.00521

Gnomad ASJ exome AF: 0.000798

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0150

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000538

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00290 AC: 4234 AN: 1461236 Hom.: 86 Cov.: 31 AF XY: 0.00309 AC XY: 2244 AN XY: 726880

Gnomad4 AFR exome AF: 0.0569

Gnomad4 AMR exome AF: 0.00496

Gnomad4 ASJ exome AF: 0.000805

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0147

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000384

Gnomad4 OTH exome AF: 0.00583

GnomAD4 genome AF: 0.0165 AC: 2511 AN: 152230 Hom.: 57 Cov.: 33 AF XY: 0.0167 AC XY: 1242 AN XY: 74434

Gnomad4 AFR AF: 0.0538

Gnomad4 AMR AF: 0.00948

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00909 Hom.: 15

Bravo AF: 0.0184

Asia WGS AF: 0.0160 AC: 55 AN: 3478

EpiCase AF: 0.000873

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.84
Dann	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000071
dbscSNV1_RF	Benign	0.0
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: rs2820135; hg19: chr1-108116661;