4-13368684-T-C

Position:

• chr4-13368684-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001017979.3(RAB28):​c.574-34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 1,560,118 control chromosomes in the GnomAD database, including 3,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (1333 hom., cov: 32)
  • Exomes 𝑓: 0.043 (2113 hom.)
• Consequence: RAB28 NM_001017979.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0770

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 4-13368684-T-C is Benign according to our data. Variant chr4-13368684-T-C is described in ClinVar as [Benign]. Clinvar id is 1280828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB28	NM_001017979.3	c.574-34A>G		intron_variant		ENST00000330852.10	NP_001017979.1
RAB28	NM_004249.4	c.*6-34A>G		intron_variant		ENST00000288723.9	NP_004240.2
RAB28	NM_001159601.2	c.*32-34A>G		intron_variant			NP_001153073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB28	ENST00000330852.10	c.574-34A>G		intron_variant		1	NM_001017979.3	ENSP00000328551.5
RAB28	ENST00000288723.9	c.*6-34A>G		intron_variant		1	NM_004249.4	ENSP00000288723.4

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14273 AN: 152116 Hom.: 1319 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0526

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0382

Gnomad OTH AF: 0.0805

GnomAD3 exomes AF: 0.0461 AC: 10708 AN: 232510 Hom.: 578 AF XY: 0.0429 AC XY: 5399 AN XY: 125988

Gnomad AFR exome AF: 0.243

Gnomad AMR exome AF: 0.0301

Gnomad ASJ exome AF: 0.0482

Gnomad EAS exome AF: 0.00101

Gnomad SAS exome AF: 0.0199

Gnomad FIN exome AF: 0.0227

Gnomad NFE exome AF: 0.0409

Gnomad OTH exome AF: 0.0367

GnomAD4 exome AF: 0.0432 AC: 60752 AN: 1407884 Hom.: 2113 Cov.: 23 AF XY: 0.0422 AC XY: 29674 AN XY: 702646

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.0315

Gnomad4 ASJ exome AF: 0.0485

Gnomad4 EAS exome AF: 0.000412

Gnomad4 SAS exome AF: 0.0214

Gnomad4 FIN exome AF: 0.0228

Gnomad4 NFE exome AF: 0.0411

Gnomad4 OTH exome AF: 0.0544

GnomAD4 genome AF: 0.0942 AC: 14333 AN: 152234 Hom.: 1333 Cov.: 32 AF XY: 0.0904 AC XY: 6726 AN XY: 74434

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.0525

Gnomad4 ASJ AF: 0.0524

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0251

Gnomad4 NFE AF: 0.0382

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0471 Hom.: 496

Bravo AF: 0.103

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.78

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: rs10003958; hg19: chr4-13370308;