chr4-13369754-C-T

Variant names:

• chr4-13369754-C-T
• rs11930851
• NM_001017979.3:c.574-1104G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 18

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• RAB28-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017979.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB28	NM_001017979.3	MANE Select	c.574-1104G>A		intron	N/A	NP_001017979.1	P51157-1
	RAB28	NM_004249.4	MANE Plus Clinical	c.*5+117G>A		intron	N/A	NP_004240.2	P51157-2
	RAB28	NM_001159601.2		c.*32-1104G>A		intron	N/A	NP_001153073.1	P51157-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB28	ENST00000330852.10	TSL:1 MANE Select	c.574-1104G>A		intron	N/A	ENSP00000328551.5	P51157-1
	RAB28	ENST00000288723.9	TSL:1 MANE Plus Clinical	c.*5+117G>A		intron	N/A	ENSP00000288723.4	P51157-2
	RAB28	ENST00000508274.5	TSL:1	n.*156-1104G>A		intron	N/A	ENSP00000424043.1	Q8WVF3

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

African (AFR) AF: 0.0619 AC: 1145 AN: 18500

American (AMR) AF: 0.00488 AC: 65 AN: 13308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14224

East Asian (EAS) AF: 0.00 AC: 0 AN: 28346

South Asian (SAS) AF: 0.000132 AC: 3 AN: 22774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28332

Middle Eastern (MID) AF: 0.00214 AC: 9 AN: 4202

European-Non Finnish (NFE) AF: 0.0000954 AC: 66 AN: 691640

Other (OTH) AF: 0.00542 AC: 201 AN: 37096

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

African (AFR) AF: 0.0587 AC: 2436 AN: 41468

American (AMR) AF: 0.00694 AC: 106 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67928

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.0166 Hom.: 8

Bravo AF: 0.0197

Asia WGS AF: 0.00549 AC: 19 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11930851; hg19: chr4-13371378;