rs10495145

Positions:

• chr1-220237104-A-T

Variant summary

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

The NM_012414.4(RAB3GAP2):​c.116-4241T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 152,276 control chromosomes in the GnomAD database, including 273 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 0.041 (273 hom., cov: 32)
• Consequence: RAB3GAP2 NM_012414.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

Genes affected

RAB3GAP2 (HGNC:17168): (RAB3 GTPase activating non-catalytic protein subunit 2) The protein encoded by this gene belongs to the RAB3 protein family, members of which are involved in regulated exocytosis of neurotransmitters and hormones. This protein forms the Rab3 GTPase-activating complex with RAB3GAP1, where it constitutes the regulatory subunit, whereas the latter functions as the catalytic subunit. This gene has the highest level of expression in the brain, consistent with it having a key role in neurodevelopment. Mutations in this gene are associated with Martsolf syndrome.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3GAP2	NM_012414.4	c.116-4241T>A		intron_variant		ENST00000358951.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3GAP2	ENST00000358951.7	c.116-4241T>A		intron_variant		1	NM_012414.4	P2

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6299 AN: 152158 Hom.: 272 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0414 AC: 6305 AN: 152276 Hom.: 273 Cov.: 32 AF XY: 0.0420 AC XY: 3124 AN XY: 74462

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.0520

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.0462

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0244 Hom.: 11

Bravo AF: 0.0480

Asia WGS AF: 0.105 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.68

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: rs10495145; hg19: chr1-220410446;