Variant 4-13369873-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BS1_SupportingBS2

The NM_004249.4(RAB28):c.*3C>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,604,714 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

RAB28
NM_004249.4 splice_region

Scores

Splicing: ADA: 0.7612

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.79

Variant links:

Genes affected

RAB28 (HGNC:9768): (RAB28, member RAS oncogene family) This gene encodes a member of the Rab subfamily of Ras-related small GTPases. The encoded protein may be involved in regulating intracellular trafficking. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 9 and X. [provided by RefSeq, Apr 2009]

RAB28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.17).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000684 (104/151994) while in subpopulation NFE AF= 0.00128 (87/67908). AF 95% confidence interval is 0.00106. There are 0 homozygotes in gnomad4. There are 48 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
RAB28	NM_004249.4 linkuse as main transcript	c.*3C>T	splice_region_variant	7/8	ENST00000288723.9	NP_004240.2	P51157-2
RAB28	NM_004249.4 linkuse as main transcript	c.*3C>T	3_prime_UTR_variant	7/8	ENST00000288723.9	NP_004240.2	P51157-2
RAB28	NM_001017979.3 linkuse as main transcript	c.574-1223C>T	intron_variant		ENST00000330852.10	NP_001017979.1	P51157-1
RAB28	NM_001159601.2 linkuse as main transcript	c.*32-1223C>T	intron_variant			NP_001153073.1	P51157-3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAB28	ENST00000288723.9 linkuse as main transcript	c.*3C>T	splice_region_variant	7/8	1	NM_004249.4	ENSP00000288723.4	P51157-2
RAB28	ENST00000288723 linkuse as main transcript	c.*3C>T	3_prime_UTR_variant	7/8	1	NM_004249.4	ENSP00000288723.4	P51157-2
RAB28	ENST00000330852.10 linkuse as main transcript	c.574-1223C>T	intron_variant		1	NM_001017979.3	ENSP00000328551.5	P51157-1

Frequencies

GnomAD3 genomes

AF:

0.000685

AC:

104

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000475

AC:

117

AN:

246446

Hom.:

AF XY:

0.000405

AC XY:

AN XY:

133200

show subpopulations

Gnomad AFR exome

AF:

0.000436

Gnomad AMR exome

AF:

0.000150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000900

Gnomad OTH exome

AF:

0.000669

GnomAD4 exome

AF:

0.00110

AC:

1597

AN:

1452720

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

780

AN XY:

722292

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.00140

Gnomad4 OTH exome

AF:

0.000583

GnomAD4 genome

AF:

0.000684

AC:

104

AN:

151994

Hom.:

Cov.:

AF XY:

0.000646

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000676

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Retinal dystrophy

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.76

dbscSNV1_RF

Benign

0.47

SpliceAI score (max)

0.34

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.34

Position offset: -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