rs2290518

Variant names:

• chr2-135121244-G-A
• rs2290518
• NM_012233.3:c.748+326G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3GAP1	NM_012233.3	MANE Select	c.748+326G>A		intron	N/A	NP_036365.1
	RAB3GAP1	NM_001172435.2		c.748+326G>A		intron	N/A	NP_001165906.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3GAP1	ENST00000264158.13	TSL:1 MANE Select	c.748+326G>A		intron	N/A	ENSP00000264158.8
	RAB3GAP1	ENST00000442034.5	TSL:1	c.748+326G>A		intron	N/A	ENSP00000411418.1
	RAB3GAP1	ENST00000688182.1		c.151-46449G>A		intron	N/A	ENSP00000509324.1

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

African (AFR) AF: 0.657 AC: 27209 AN: 41432

American (AMR) AF: 0.326 AC: 4974 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 858 AN: 3468

East Asian (EAS) AF: 0.304 AC: 1571 AN: 5164

South Asian (SAS) AF: 0.379 AC: 1821 AN: 4804

European-Finnish (FIN) AF: 0.138 AC: 1454 AN: 10572

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9066 AN: 67974

Other (OTH) AF: 0.299 AC: 631 AN: 2108

Alfa AF: 0.182 Hom.: 2538

Bravo AF: 0.339

Asia WGS AF: 0.367 AC: 1275 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.62
PhyloP100		-0.22
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: rs2290518; hg19: chr2-135878814;