chr2-135100360-A-G

Position:

• chr2-135100360-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012233.3(RAB3GAP1):​c.362+6667A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 152,334 control chromosomes in the GnomAD database, including 90 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 0.028 (90 hom., cov: 32)
• Consequence: RAB3GAP1 NM_012233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0278 (4230/152334) while in subpopulation SAS AF= 0.0495 (239/4830). AF 95% confidence interval is 0.0443. There are 90 homozygotes in gnomad4. There are 2242 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 90 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB3GAP1	NM_012233.3	c.362+6667A>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.362+6667A>G		intron_variant		1	NM_012233.3	ENSP00000264158	A1

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4232 AN: 152216 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.00632

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0518

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.0615

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0267

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

GnomAD4 genome AF: 0.0278 AC: 4230 AN: 152334 Hom.: 90 Cov.: 32 AF XY: 0.0301 AC XY: 2242 AN XY: 74500

Gnomad4 AFR AF: 0.00630

Gnomad4 AMR AF: 0.0404

Gnomad4 ASJ AF: 0.0518

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0495

Gnomad4 FIN AF: 0.0615

Gnomad4 NFE AF: 0.0325

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0344 Hom.: 92

Bravo AF: 0.0243

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0050
DANN	Benign	0.46

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: rs1031575; hg19: chr2-135857930;