Variant 2-135052620-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012233.3(RAB3GAP1):c.74+135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,041,032 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 6 hom. )

Consequence

RAB3GAP1
NM_012233.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.51

Variant links:

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]

RAB3GAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-135052620-C-T is Benign according to our data. Variant chr2-135052620-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1214238.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00475 (724/152268) while in subpopulation AFR AF= 0.0146 (606/41548). AF 95% confidence interval is 0.0136. There are 2 homozygotes in gnomad4. There are 359 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB3GAP1	NM_012233.3 linkuse as main transcript	c.74+135C>T		intron_variant		ENST00000264158.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB3GAP1	ENST00000264158.13 linkuse as main transcript	c.74+135C>T		intron_variant		1	NM_012233.3	A1	Q15042-1

Frequencies

GnomAD3 genomes

AF:

0.00469

AC:

714

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00335

GnomAD4 exome

AF:

0.00118

AC:

1053

AN:

888764

Hom.:

AF XY:

0.00117

AC XY:

537

AN XY:

458248

show subpopulations

Gnomad4 AFR exome

AF:

0.0133

Gnomad4 AMR exome

AF:

0.00147

Gnomad4 ASJ exome

AF:

0.0171

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000284

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000351

Gnomad4 OTH exome

AF:

0.00260

GnomAD4 genome

AF:

0.00475

AC:

724

AN:

152268

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

359

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000420

Hom.:

Bravo

AF:

0.00566

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.017

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over