1-107572523-T-C

Variant names:

• chr1-107572523-T-C
• rs2769668
• NM_006113.5:c.*808A>G

Variant summary

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

The ENST00000370056.9(VAV3):​c.*808A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,666 control chromosomes in the GnomAD database, including 62,546 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 0.90 (62343 hom., cov: 32)
  • Exomes 𝑓: 0.96 (203 hom.)
• Consequence: VAV3 ENST00000370056.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370056.9. 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
	VAV3	NM_006113.5	MANE Select	c.*808A>G		3_prime_UTR	Exon 27 of 27	NP_006104.4
	VAV3	NM_001079874.2		c.*808A>G		3_prime_UTR	Exon 10 of 10	NP_001073343.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV3	ENST00000370056.9	TSL:1 MANE Select	c.*808A>G		3_prime_UTR	Exon 27 of 27	ENSP00000359073.4
	VAV3	ENST00000527011.5	TSL:1	c.*808A>G		3_prime_UTR	Exon 28 of 28	ENSP00000432540.1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137374 AN: 152112 Hom.: 62312 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.933

Gnomad OTH AF: 0.914

GnomAD4 exome AF: 0.963 AC: 420 AN: 436 Hom.: 203 Cov.: 0 AF XY: 0.966 AC XY: 255 AN XY: 264

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.962 AC: 408 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 8 AN: 8

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.903 AC: 137461 AN: 152230 Hom.: 62343 Cov.: 32 AF XY: 0.906 AC XY: 67414 AN XY: 74430

African (AFR) AF: 0.807 AC: 33478 AN: 41504

American (AMR) AF: 0.947 AC: 14502 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3181 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5178 AN: 5182

South Asian (SAS) AF: 0.938 AC: 4516 AN: 4816

European-Finnish (FIN) AF: 0.951 AC: 10084 AN: 10604

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.933 AC: 63496 AN: 68024

Other (OTH) AF: 0.915 AC: 1936 AN: 2116

Alfa AF: 0.923 Hom.: 81088

Bravo AF: 0.899

Asia WGS AF: 0.957 AC: 3329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.18
DANN	Benign	0.46
PhyloP100		-1.6
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: rs2769668; hg19: chr1-108115145;