1-107814198-A-G

Variant names:

• chr1-107814198-A-G
• rs12126655
• NM_006113.5:c.322-34706T>C

Variant summary

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

The NM_006113.5(VAV3):​c.322-34706T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,912 control chromosomes in the GnomAD database, including 8,269 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 0.33 (8269 hom., cov: 31)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006113.5. 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
	VAV3	NM_006113.5	MANE Select	c.322-34706T>C		intron	N/A	NP_006104.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV3	ENST00000370056.9	TSL:1 MANE Select	c.322-34706T>C		intron	N/A	ENSP00000359073.4	Q9UKW4-1
	VAV3	ENST00000527011.5	TSL:1	c.322-34706T>C		intron	N/A	ENSP00000432540.1	Q9UKW4-4
	VAV3	ENST00000923907.1		c.322-34706T>C		intron	N/A	ENSP00000593966.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49763 AN: 151794 Hom.: 8254 Cov.: 31

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.328 AC: 49818 AN: 151912 Hom.: 8269 Cov.: 31 AF XY: 0.325 AC XY: 24111 AN XY: 74272

African (AFR) AF: 0.352 AC: 14580 AN: 41386

American (AMR) AF: 0.319 AC: 4872 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1384 AN: 3470

East Asian (EAS) AF: 0.308 AC: 1591 AN: 5168

South Asian (SAS) AF: 0.356 AC: 1715 AN: 4818

European-Finnish (FIN) AF: 0.243 AC: 2563 AN: 10566

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21964 AN: 67924

Other (OTH) AF: 0.307 AC: 648 AN: 2110

Alfa AF: 0.331 Hom.: 26123

Bravo AF: 0.338

Asia WGS AF: 0.342 AC: 1188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.31
PhyloP100		-0.45
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: rs12126655; hg19: chr1-108356820;