rs9291610

Positions:

• chr4-13372838-G-A

Variant summary

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

The NM_001017979.3(RAB28):​c.573+3707C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.094 in 151,930 control chromosomes in the GnomAD database, including 1,322 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 0.094 (1322 hom., cov: 32)
• Consequence: RAB28 NM_001017979.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAB28	NM_001017979.3	c.573+3707C>T		intron_variant		ENST00000330852.10
RAB28	NM_004249.4	c.574-2873C>T		intron_variant		ENST00000288723.9
RAB28	NM_001159601.2	c.574-971C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAB28	ENST00000288723.9	c.574-2873C>T		intron_variant		1	NM_004249.4	A1
RAB28	ENST00000330852.10	c.573+3707C>T		intron_variant		1	NM_001017979.3	P4

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14228 AN: 151812 Hom.: 1308 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.0940 AC: 14288 AN: 151930 Hom.: 1322 Cov.: 32 AF XY: 0.0904 AC XY: 6713 AN XY: 74288

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.0527

Gnomad4 ASJ AF: 0.0525

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0251

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.0787

Alfa AF: 0.0612 Hom.: 111

Bravo AF: 0.103

Asia WGS AF: 0.0290 AC: 103 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.13

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: rs9291610; hg19: chr4-13374462;