rs7570971

chr2-135080336-C-Achr2-135080336-C-Gchr2-135080336-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012233.3(RAB3GAP1):c.151-10662C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,024 control chromosomes in the GnomAD database, including 33,904 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 0.61 (33904 hom., cov: 31)
• Consequence: RAB3GAP1 NM_012233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

Genes affected

RAB3GAP1 (HGNC:17063): (RAB3 GTPase activating protein catalytic subunit 1) This gene encodes the catalytic subunit of a Rab GTPase activating protein. The encoded protein forms a heterodimer with a non-catalytic subunit to specifically regulate the activity of members of the Rab3 subfamily of small G proteins. This protein mediates the hydrolysis of GTP bound Rab3 to the GDP bound form. Mutations in this gene are associated with Warburg micro syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3GAP1	NM_012233.3	c.151-10662C>A		intron_variant		ENST00000264158.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3GAP1	ENST00000264158.13	c.151-10662C>A		intron_variant		1	NM_012233.3	A1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93233 AN: 151906 Hom.: 33837 Cov.: 31

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.614 AC: 93364 AN: 152024 Hom.: 33904 Cov.: 31 AF XY: 0.629 AC XY: 46737 AN XY: 74320

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.714

Alfa AF: 0.476 Hom.: 21605

Bravo AF: 0.652

Asia WGS AF: 0.929 AC: 3229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.7
Dann	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs7570971; hg19: chr2-135837906;