NM_001017979.3:c.573+3707C>T

Variant names:

• chr4-13372838-G-A
• rs9291610
• NM_001017979.3:c.573+3707C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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.

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.573+3707C>T		intron	N/A	NP_001017979.1	P51157-1
	RAB28	NM_004249.4	MANE Plus Clinical	c.574-2873C>T		intron	N/A	NP_004240.2	P51157-2
	RAB28	NM_001159601.2		c.574-971C>T		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.573+3707C>T		intron	N/A	ENSP00000328551.5	P51157-1
	RAB28	ENST00000288723.9	TSL:1 MANE Plus Clinical	c.574-2873C>T		intron	N/A	ENSP00000288723.4	P51157-2
	RAB28	ENST00000508274.5	TSL:1	n.*155+3707C>T		intron	N/A	ENSP00000424043.1	Q8WVF3

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

African (AFR) AF: 0.244 AC: 10115 AN: 41420

American (AMR) AF: 0.0527 AC: 803 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0525 AC: 182 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.0174 AC: 84 AN: 4822

European-Finnish (FIN) AF: 0.0251 AC: 266 AN: 10602

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0381 AC: 2589 AN: 67886

Other (OTH) AF: 0.0787 AC: 166 AN: 2110

Alfa AF: 0.0655 Hom.: 136

Bravo AF: 0.103

Asia WGS AF: 0.0290 AC: 103 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.13
PhyloP100		-0.61
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: rs9291610; hg19: chr4-13374462;