19-10013026-C-T

Variant names:

• chr19-10013026-C-T
• rs2233789
• ENST00000651512.1:c.-412C>T

Variant summary

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

The ENST00000651512.1(RDH8):​c.-412C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,970 control chromosomes in the GnomAD database, including 8,195 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 0.30 (8195 hom., cov: 32)
• Consequence: RDH8 ENST00000651512.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 2 publications found

Genes affected

RDH8 (HGNC:14423): (retinol dehydrogenase 8) This gene encodes a member of the short-chain dehydrogenase/reductase family. The encoded protein catalyzes the reduction of all-trans-retinal to all-trans-retinol, the first reaction step of the rhodopsin regeneration pathway. This enzymatic reaction is the rate-limiting step in the visual cycle. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651512.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH8	ENST00000651512.1		c.-412C>T		upstream_gene	N/A	ENSP00000498711.1	K7ELF7

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45615 AN: 151854 Hom.: 8197 Cov.: 32

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.300 AC: 45620 AN: 151970 Hom.: 8195 Cov.: 32 AF XY: 0.303 AC XY: 22478 AN XY: 74252

African (AFR) AF: 0.0897 AC: 3719 AN: 41478

American (AMR) AF: 0.329 AC: 5030 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1440 AN: 3470

East Asian (EAS) AF: 0.343 AC: 1775 AN: 5172

South Asian (SAS) AF: 0.340 AC: 1640 AN: 4818

European-Finnish (FIN) AF: 0.419 AC: 4405 AN: 10514

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26433 AN: 67940

Other (OTH) AF: 0.350 AC: 738 AN: 2106

Alfa AF: 0.198 Hom.: 457

Bravo AF: 0.287

Asia WGS AF: 0.273 AC: 950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.99
DANN	Benign	0.34
PhyloP100		-2.4
PromoterAI		-0.014	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2233789;

hg19: chr19-10123702;