19-10022183-T-A

Variant names:

• chr19-10022183-T-A
• rs1644730
• NM_015725.4:c.*434T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-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 rank	MANE	Protein	UniProt
RDH8	NM_015725.4	c.*434T>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000591589.3	NP_056540.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RDH8	ENST00000591589.3	c.*434T>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_015725.4	ENSP00000466058.2
RDH8	ENST00000651512.1	c.*434T>A		3_prime_UTR_variant	Exon 6 of 6			ENSP00000498711.1
RDH8	ENST00000587782.1	c.*577T>A		downstream_gene_variant		2		ENSP00000465773.1

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

African (AFR) AF: 0.589 AC: 246 AN: 418

American (AMR) AF: 0.537 AC: 1404 AN: 2616

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 154 AN: 352

East Asian (EAS) AF: 0.486 AC: 384 AN: 790

South Asian (SAS) AF: 0.629 AC: 944 AN: 1500

European-Finnish (FIN) AF: 0.415 AC: 175 AN: 422

Middle Eastern (MID) AF: 0.250 AC: 6 AN: 24

European-Non Finnish (NFE) AF: 0.391 AC: 4085 AN: 10448

Other (OTH) AF: 0.434 AC: 375 AN: 864

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

African (AFR) AF: 0.613 AC: 25333 AN: 41358

American (AMR) AF: 0.545 AC: 8289 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1638 AN: 3466

East Asian (EAS) AF: 0.549 AC: 2835 AN: 5160

South Asian (SAS) AF: 0.678 AC: 3254 AN: 4800

European-Finnish (FIN) AF: 0.548 AC: 5759 AN: 10510

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30417 AN: 67894

Other (OTH) AF: 0.517 AC: 1089 AN: 2108

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
PhyloP100		0.33
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: rs1644730; hg19: chr19-10132859;