4-13369754-C-T

Position:

• chr4-13369754-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001017979.3(RAB28):​c.574-1104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,010,452 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (82 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (44 hom.)
• Consequence: RAB28 NM_001017979.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.233

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 4-13369754-C-T is Benign according to our data. Variant chr4-13369754-C-T is described in ClinVar as [Benign]. Clinvar id is 1302795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB28	NM_001017979.3	c.574-1104G>A		intron_variant		ENST00000330852.10	NP_001017979.1
RAB28	NM_004249.4	c.*5+117G>A		intron_variant		ENST00000288723.9	NP_004240.2
RAB28	NM_001159601.2	c.*32-1104G>A		intron_variant			NP_001153073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB28	ENST00000330852.10	c.574-1104G>A		intron_variant		1	NM_001017979.3	ENSP00000328551.5
RAB28	ENST00000288723.9	c.*5+117G>A		intron_variant		1	NM_004249.4	ENSP00000288723.4

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2568 AN: 151912 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00695

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00173 AC: 1489 AN: 858422 Hom.: 44 AF XY: 0.00162 AC XY: 676 AN XY: 418270

Gnomad4 AFR exome AF: 0.0619

Gnomad4 AMR exome AF: 0.00488

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000132

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000954

Gnomad4 OTH exome AF: 0.00542

GnomAD4 genome AF: 0.0170 AC: 2582 AN: 152030 Hom.: 82 Cov.: 32 AF XY: 0.0165 AC XY: 1224 AN XY: 74310

Gnomad4 AFR AF: 0.0587

Gnomad4 AMR AF: 0.00694

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0147 Hom.: 7

Bravo AF: 0.0197

Asia WGS AF: 0.00549 AC: 19 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.72

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: rs11930851; hg19: chr4-13371378;