rs2305248

Variant names:

• chr2-135170742-A-G
• rs2305248
• ENST00000412849.5:n.1782-5588T>C

Variant summary

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

The ENST00000619650.4(ZRANB3):​c.1618-5588T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,028 control chromosomes in the GnomAD database, including 11,201 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 (11201 hom., cov: 31)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: ZRANB3 ENST00000619650.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

Genes affected

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]

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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB3GAP1	NM_012233.3	c.*1961A>G		downstream_gene_variant		ENST00000264158.13	NP_036365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB3GAP1	ENST00000264158.13	c.*1961A>G		downstream_gene_variant		1	NM_012233.3	ENSP00000264158.8

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47312 AN: 151900 Hom.: 11161 Cov.: 31

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.312 AC: 47408 AN: 152018 Hom.: 11201 Cov.: 31 AF XY: 0.314 AC XY: 23309 AN XY: 74296

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.301

Alfa AF: 0.184 Hom.: 2391

Bravo AF: 0.337

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2305248; hg19: chr2-135928312;