chr2-135080336-C-A

Variant names:

• chr2-135080336-C-A
• rs7570971
• NM_012233.3:c.151-10662C>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.151-10662C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,024 control chromosomes in the GnomAD database, including 33,904 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 0.61 (33904 hom., cov: 31)
• Consequence: RAB3GAP1 NM_012233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 82 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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.151-10662C>A		intron	N/A	NP_036365.1
	RAB3GAP1	NM_001172435.2		c.151-10662C>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.151-10662C>A		intron	N/A	ENSP00000264158.8
	RAB3GAP1	ENST00000442034.5	TSL:1	c.151-10662C>A		intron	N/A	ENSP00000411418.1
	RAB3GAP1	ENST00000688182.1		c.150+22250C>A		intron	N/A	ENSP00000509324.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93233 AN: 151906 Hom.: 33837 Cov.: 31

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.614 AC: 93364 AN: 152024 Hom.: 33904 Cov.: 31 AF XY: 0.629 AC XY: 46737 AN XY: 74320

African (AFR) AF: 0.882 AC: 36633 AN: 41520

American (AMR) AF: 0.782 AC: 11943 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3038 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5163 AN: 5174

South Asian (SAS) AF: 0.838 AC: 4048 AN: 4830

European-Finnish (FIN) AF: 0.429 AC: 4512 AN: 10516

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 25987 AN: 67924

Other (OTH) AF: 0.714 AC: 1507 AN: 2112

Alfa AF: 0.477 Hom.: 61123

Bravo AF: 0.652

Asia WGS AF: 0.929 AC: 3229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.7
DANN	Benign	0.38
PhyloP100		-0.019
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: rs7570971; hg19: chr2-135837906;