rs56786863

Variant names:

• chr2-135162538-C-T
• rs56786863
• NM_012233.3:c.2290-17C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012233.3(RAB3GAP1):​c.2290-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,590,360 control chromosomes in the GnomAD database, including 1,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (528 hom., cov: 32)
  • Exomes 𝑓: 0.023 (902 hom.)
• Consequence: RAB3GAP1 NM_012233.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.67
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-135162538-C-T is Benign according to our data. Variant chr2-135162538-C-T is described in ClinVar as Benign. ClinVar VariationId is 138860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3GAP1	NM_012233.3	MANE Select	c.2290-17C>T		intron	N/A	NP_036365.1	B9A6J2
	RAB3GAP1	NM_001172435.2		c.2290-17C>T		intron	N/A	NP_001165906.1	Q15042-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB3GAP1	ENST00000264158.13	TSL:1 MANE Select	c.2290-17C>T		intron	N/A	ENSP00000264158.8	Q15042-1
	RAB3GAP1	ENST00000442034.5	TSL:1	c.2290-17C>T		intron	N/A	ENSP00000411418.1	Q15042-3
	ZRANB3	ENST00000412849.5	TSL:1	n.1883G>A		non_coding_transcript_exon	Exon 12 of 14

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9212 AN: 152008 Hom.: 528 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0535

GnomAD2 exomes AF: 0.0346 AC: 8535 AN: 246450 AF XY: 0.0311

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.0399

Gnomad ASJ exome AF: 0.0661

Gnomad EAS exome AF: 0.0490

Gnomad FIN exome AF: 0.0178

Gnomad NFE exome AF: 0.0207

Gnomad OTH exome AF: 0.0307

GnomAD4 exome AF: 0.0229 AC: 32889 AN: 1438234 Hom.: 902 Cov.: 28 AF XY: 0.0229 AC XY: 16397 AN XY: 716454

African (AFR) AF: 0.155 AC: 5109 AN: 33054

American (AMR) AF: 0.0389 AC: 1729 AN: 44396

Ashkenazi Jewish (ASJ) AF: 0.0702 AC: 1819 AN: 25898

East Asian (EAS) AF: 0.0536 AC: 2120 AN: 39546

South Asian (SAS) AF: 0.0120 AC: 1027 AN: 85292

European-Finnish (FIN) AF: 0.0176 AC: 933 AN: 53160

Middle Eastern (MID) AF: 0.0239 AC: 137 AN: 5726

European-Non Finnish (NFE) AF: 0.0166 AC: 18125 AN: 1091584

Other (OTH) AF: 0.0317 AC: 1890 AN: 59578

GnomAD4 genome AF: 0.0607 AC: 9229 AN: 152126 Hom.: 528 Cov.: 32 AF XY: 0.0587 AC XY: 4367 AN XY: 74376

African (AFR) AF: 0.153 AC: 6323 AN: 41442

American (AMR) AF: 0.0422 AC: 645 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3472

East Asian (EAS) AF: 0.0570 AC: 295 AN: 5172

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4828

European-Finnish (FIN) AF: 0.0140 AC: 148 AN: 10594

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0211 AC: 1432 AN: 68016

Other (OTH) AF: 0.0539 AC: 114 AN: 2116

Alfa AF: 0.0496 Hom.: 110

Bravo AF: 0.0669

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.18
DANN	Benign	0.48
PhyloP100		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs56786863; hg19: chr2-135920108;