rs4954221

Positions:

• chr2-135151892-G-A

Variant summary

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

The NM_012233.3(RAB3GAP1):​c.2061+1386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,106 control chromosomes in the GnomAD database, including 11,370 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 (11370 hom., cov: 32)
• Consequence: RAB3GAP1 NM_012233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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]

ZRANB3 (HGNC:):

ZRANB3 (HGNC:25249): (zinc finger RANBP2-type containing 3) Enables ATP-dependent DNA/DNA annealing activity; K63-linked polyubiquitin modification-dependent protein binding activity; and endodeoxyribonuclease activity. Involved in several processes, including DNA metabolic process; DNA rewinding; and negative regulation of DNA recombination. Located in nuclear replication fork and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB3GAP1	NM_012233.3	c.2061+1386G>A		intron_variant		ENST00000264158.13	NP_036365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB3GAP1	ENST00000264158.13	c.2061+1386G>A		intron_variant		1	NM_012233.3	ENSP00000264158.8

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47506 AN: 151988 Hom.: 11323 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.313 AC: 47609 AN: 152106 Hom.: 11370 Cov.: 32 AF XY: 0.315 AC XY: 23418 AN XY: 74376

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.298

Alfa AF: 0.181 Hom.: 2438

Bravo AF: 0.338

Asia WGS AF: 0.373 AC: 1296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
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: rs4954221; hg19: chr2-135909462;