rs1869829

Variant names:

• chr2-135119992-A-G
• rs1869829
• NM_012233.3:c.649-827A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• Warburg micro syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Warburg micro syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• cataract-intellectual disability-hypogonadism syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012233.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3GAP1	NM_012233.3	MANE Select	c.649-827A>G		intron	N/A	NP_036365.1	B9A6J2
	RAB3GAP1	NM_001172435.2		c.649-827A>G		intron	N/A	NP_001165906.1	Q15042-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3GAP1	ENST00000264158.13	TSL:1 MANE Select	c.649-827A>G		intron	N/A	ENSP00000264158.8	Q15042-1
	RAB3GAP1	ENST00000442034.5	TSL:1	c.649-827A>G		intron	N/A	ENSP00000411418.1	Q15042-3
	RAB3GAP1	ENST00000970735.1		c.652-827A>G		intron	N/A	ENSP00000640794.1

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

African (AFR) AF: 0.839 AC: 34815 AN: 41510

American (AMR) AF: 0.574 AC: 8786 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2244 AN: 3462

East Asian (EAS) AF: 0.697 AC: 3610 AN: 5176

South Asian (SAS) AF: 0.683 AC: 3292 AN: 4820

European-Finnish (FIN) AF: 0.282 AC: 2974 AN: 10560

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19140 AN: 67944

Other (OTH) AF: 0.545 AC: 1152 AN: 2112

Alfa AF: 0.380 Hom.: 6625

Bravo AF: 0.533

Asia WGS AF: 0.713 AC: 2474 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.69
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1869829; hg19: chr2-135877562;