rs6730157

Variant names:

• chr2-135149518-A-G
• rs6730157
• NM_012233.3:c.1924-851A>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.1924-851A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,136 control chromosomes in the GnomAD database, including 33,638 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 (33638 hom., cov: 32)
• Consequence: RAB3GAP1 NM_012233.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 41 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]

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB3GAP1	NM_012233.3	c.1924-851A>G		intron_variant	Intron 17 of 23	ENST00000264158.13	NP_036365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB3GAP1	ENST00000264158.13	c.1924-851A>G		intron_variant	Intron 17 of 23	1	NM_012233.3	ENSP00000264158.8

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92782 AN: 152018 Hom.: 33572 Cov.: 32

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.611 AC: 92912 AN: 152136 Hom.: 33638 Cov.: 32 AF XY: 0.625 AC XY: 46515 AN XY: 74380

African (AFR) AF: 0.881 AC: 36602 AN: 41532

American (AMR) AF: 0.779 AC: 11902 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3024 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5169 AN: 5180

South Asian (SAS) AF: 0.823 AC: 3976 AN: 4830

European-Finnish (FIN) AF: 0.426 AC: 4499 AN: 10556

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25710 AN: 67968

Other (OTH) AF: 0.709 AC: 1498 AN: 2112

Alfa AF: 0.522 Hom.: 51758

Bravo AF: 0.649

Asia WGS AF: 0.924 AC: 3212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.82
DANN	Benign	0.45
PhyloP100		-1.4
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: rs6730157; hg19: chr2-135907088;