rs1644730

Positions:

• chr19-10022183-T-A
• chr19-10022183-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015725.4(RDH8):​c.*434T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 169,150 control chromosomes in the GnomAD database, including 23,015 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 0.52 (21099 hom., cov: 31)
  • Exomes 𝑓: 0.45 (1916 hom.)
• Consequence: RDH8 NM_015725.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RDH8	NM_015725.4	c.*434T>A		3_prime_UTR_variant	6/6	ENST00000591589.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RDH8	ENST00000591589.3	c.*434T>A		3_prime_UTR_variant	6/6	1	NM_015725.4	P1
RDH8	ENST00000651512.1	c.*434T>A		3_prime_UTR_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79048 AN: 151598 Hom.: 21070 Cov.: 31

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.446 AC: 7773 AN: 17434 Hom.: 1916 Cov.: 0 AF XY: 0.445 AC XY: 3993 AN XY: 8970

Gnomad4 AFR exome AF: 0.589

Gnomad4 AMR exome AF: 0.537

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.415

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.434

GnomAD4 genome AF: 0.522 AC: 79138 AN: 151716 Hom.: 21099 Cov.: 31 AF XY: 0.528 AC XY: 39146 AN XY: 74130

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.517

Alfa AF: 0.469 Hom.: 2151

Bravo AF: 0.521

Asia WGS AF: 0.636 AC: 2213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.77

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: rs1644730; hg19: chr19-10132859;