2-135119992-A-G

Position:

• chr2-135119992-A-G

Variant summary

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

The NM_012233.3(RAB3GAP1):​c.649-827A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,082 control chromosomes in the GnomAD database, including 24,200 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 0.50 (24200 hom., cov: 33)
• Consequence: RAB3GAP1 NM_012233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307

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]

RAB3GAP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB3GAP1	NM_012233.3	c.649-827A>G		intron_variant		ENST00000264158.13	NP_036365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB3GAP1	ENST00000264158.13	c.649-827A>G		intron_variant		1	NM_012233.3	ENSP00000264158.8

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76266 AN: 151964 Hom.: 24132 Cov.: 33

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.502 AC: 76400 AN: 152082 Hom.: 24200 Cov.: 33 AF XY: 0.510 AC XY: 37903 AN XY: 74330

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.545

Alfa AF: 0.381 Hom.: 5845

Bravo AF: 0.533

Asia WGS AF: 0.713 AC: 2474 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1869829; hg19: chr2-135877562;