rs2305594

chr2-135133038-G-C

Variant summary

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

The NM_012233.3(RAB3GAP1):c.1326+54G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,068,816 control chromosomes in the GnomAD database, including 9,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1294 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8153 hom.)
• Consequence: RAB3GAP1 NM_012233.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.446

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-135133038-G-C is Benign according to our data. Variant chr2-135133038-G-C is described in ClinVar as [Benign]. Clinvar id is 1222267.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3GAP1	NM_012233.3	c.1326+54G>C		intron_variant		ENST00000264158.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3GAP1	ENST00000264158.13	c.1326+54G>C		intron_variant		1	NM_012233.3	A1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17408 AN: 151984 Hom.: 1299 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.107 AC: 98432 AN: 916714 Hom.: 8153 AF XY: 0.115 AC XY: 54942 AN XY: 478746

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.0598

Gnomad4 NFE exome AF: 0.0737

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.114 AC: 17415 AN: 152102 Hom.: 1294 Cov.: 32 AF XY: 0.119 AC XY: 8867 AN XY: 74358

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.0630

Gnomad4 NFE AF: 0.0794

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0940 Hom.: 102

Bravo AF: 0.121

Asia WGS AF: 0.286 AC: 990 AN: 3470

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

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.3
Dann	Benign	0.56

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: rs2305594; hg19: chr2-135890608;