NM_001017979.3:c.391+33675C>G

Variant names:

• chr4-13427024-G-C
• rs10516267
• NM_001017979.3:c.391+33675C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017979.3(RAB28):​c.391+33675C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 152,168 control chromosomes in the GnomAD database, including 542 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 0.056 (542 hom., cov: 32)
• Consequence: RAB28 NM_001017979.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 2 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 Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB28	NM_001017979.3	c.391+33675C>G		intron_variant	Intron 4 of 6	ENST00000330852.10	NP_001017979.1
RAB28	NM_004249.4	c.391+33675C>G		intron_variant	Intron 4 of 7	ENST00000288723.9	NP_004240.2
RAB28	NM_001159601.2	c.391+33675C>G		intron_variant	Intron 4 of 7		NP_001153073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB28	ENST00000330852.10	c.391+33675C>G		intron_variant	Intron 4 of 6	1	NM_001017979.3	ENSP00000328551.5
RAB28	ENST00000288723.9	c.391+33675C>G		intron_variant	Intron 4 of 7	1	NM_004249.4	ENSP00000288723.4

Frequencies

GnomAD3 genomes AF: 0.0554 AC: 8426 AN: 152050 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0557 AC: 8479 AN: 152168 Hom.: 542 Cov.: 32 AF XY: 0.0527 AC XY: 3924 AN XY: 74394

African (AFR) AF: 0.156 AC: 6464 AN: 41526

American (AMR) AF: 0.0261 AC: 399 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.00974 AC: 47 AN: 4824

European-Finnish (FIN) AF: 0.0195 AC: 206 AN: 10588

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1224 AN: 67984

Other (OTH) AF: 0.0427 AC: 90 AN: 2110

Alfa AF: 0.0394 Hom.: 35

Bravo AF: 0.0613

Asia WGS AF: 0.0190 AC: 65 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.49
DANN	Benign	0.39
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs10516267; hg19: chr4-13428648;