Variant rs45459199 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_016277.5(RAB23):c.574+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00895 in 1,609,212 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0096 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0089 ( 110 hom. )

Consequence

RAB23
NM_016277.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.519

Variant links:

Genes affected

RAB23 (HGNC:14263): (RAB23, member RAS oncogene family) This gene encodes a small GTPase of the Ras superfamily. Rab proteins are involved in the regulation of diverse cellular functions associated with intracellular membrane trafficking, including autophagy and immune response to bacterial infection. The encoded protein may play a role in central nervous system development by antagonizing sonic hedgehog signaling. Disruption of this gene has been implicated in Carpenter syndrome as well as cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RAB23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 6-57193814-C-T is Benign according to our data. Variant chr6-57193814-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1201159.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00965 (1468/152166) while in subpopulation NFE AF= 0.0119 (812/67968). AF 95% confidence interval is 0.0113. There are 22 homozygotes in gnomad4. There are 823 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB23	NM_016277.5 linkuse as main transcript	c.574+28G>A		intron_variant		ENST00000468148.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB23	ENST00000468148.6 linkuse as main transcript	c.574+28G>A		intron_variant		1	NM_016277.5	P1
RAB23	ENST00000317483.4 linkuse as main transcript	c.574+28G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes

AF:

0.00965

AC:

1468

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0463

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00673

GnomAD3 exomes

AF:

0.0100

AC:

2470

AN:

247004

Hom.:

AF XY:

0.00998

AC XY:

1330

AN XY:

133288

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.00270

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000375

Gnomad FIN exome

AF:

0.0422

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.00747

GnomAD4 exome

AF:

0.00888

AC:

12939

AN:

1457046

Hom.:

110

Cov.:

AF XY:

0.00877

AC XY:

6353

AN XY:

724510

show subpopulations

Gnomad4 AFR exome

AF:

0.000719

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000400

Gnomad4 FIN exome

AF:

0.0379

Gnomad4 NFE exome

AF:

0.00902

Gnomad4 OTH exome

AF:

0.00741

GnomAD4 genome

AF:

0.00965

AC:

1468

AN:

152166

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

823

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00406

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0463

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00666

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.00587

Asia WGS

AF:

0.000579

AC:

AN:

3466

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

Feb 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.55

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