Variant 4-139453833-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The ENST00000652268.1(RAB33B):c.125+136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00386 in 180,866 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0045 ( 6 hom., cov: 33)

Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

RAB33B
ENST00000652268.1 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0530

Variant links:

Genes affected

RAB33B (HGNC:16075): (RAB33B, member RAS oncogene family) This gene encodes a small GTP-binding protein of the Rab GTPase family, whose members function in vesicle transport during protein secretion and endocytosis. Rab GTPases are active, membrane-associated proteins that recruit effector proteins in the GTP-bound state and inactive cytosolic proteins when in a GDP-bound state. The protein encoded by this gene is ubiquitously expressed and has been implicated in Golgi to endoplasmic reticulum cycling of Golgi enzymes. In addition, this protein regulates Golgi homeostasis and coordinates intra-Golgi retrograde trafficking. Allelic variants in this gene have been associated with Dyggve-Melchior-Clausen syndrome and Smith-McCort dysplasia 2, which are autosomal recessive spondyloepimetaphyseal dysplasias characterized by skeletal abnormalities. [provided by RefSeq, Sep 2016]

RAB33B links:

RAB33B-AS1 (HGNC:):

RAB33B-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0045 (685/152326) while in subpopulation AFR AF= 0.0147 (612/41580). AF 95% confidence interval is 0.0138. There are 6 homozygotes in gnomad4. There are 329 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	UniProt
RAB33B	XM_011532299.2 linkuse as main transcript	c.125+136G>A	intron_variant		XP_011530601.1	A0A494C0Z5
RAB33B-AS1	NR_159963.1 linkuse as main transcript	n.209C>T	non_coding_transcript_exon_variant	1/2
RAB33B-AS1	NR_159964.1 linkuse as main transcript	n.209C>T	non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
RAB33B	ENST00000652268.1 linkuse as main transcript	c.125+136G>A	intron_variant			ENSP00000498778.1	A0A494C0Z5
RAB33B-AS1	ENST00000608661.1 linkuse as main transcript	n.123C>T	non_coding_transcript_exon_variant	1/3	5
RAB33B-AS1	ENST00000609359.1 linkuse as main transcript	n.202C>T	non_coding_transcript_exon_variant	1/3	2
RAB33B	ENST00000507271.1 linkuse as main transcript	n.466+136G>A	intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00451

AC:

686

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00335

GnomAD4 exome

AF:

0.000491

AC:

AN:

28540

Hom.:

Cov.:

AF XY:

0.000552

AC XY:

AN XY:

14498

show subpopulations

Gnomad4 AFR exome

AF:

0.00822

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000509

Gnomad4 OTH exome

AF:

0.000506

GnomAD4 genome

AF:

0.00450

AC:

685

AN:

152326

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

329

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0147

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00347

Hom.:

Bravo

AF:

0.00508

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Smith-McCort dysplasia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.86

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