rs2290518

Positions:

• chr2-135121244-G-A

Variant summary

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

The NM_012233.3(RAB3GAP1):​c.748+326G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,006 control chromosomes in the GnomAD database, including 11,436 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 0.31 (11436 hom., cov: 32)
• Consequence: RAB3GAP1 NM_012233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3GAP1	NM_012233.3	c.748+326G>A		intron_variant		ENST00000264158.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3GAP1	ENST00000264158.13	c.748+326G>A		intron_variant		1	NM_012233.3	A1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47627 AN: 151888 Hom.: 11389 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.314 AC: 47730 AN: 152006 Hom.: 11436 Cov.: 32 AF XY: 0.316 AC XY: 23478 AN XY: 74294

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.299

Alfa AF: 0.185 Hom.: 2411

Bravo AF: 0.339

Asia WGS AF: 0.367 AC: 1275 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.62

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: rs2290518; hg19: chr2-135878814;