19-10022183-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015725.4(RDH8):​c.*434T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015725.4. 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
	RDH8	NM_015725.4	MANE Select	c.*434T>G		3_prime_UTR	Exon 6 of 6	NP_056540.3	Q9NYR8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH8	ENST00000591589.3	TSL:1 MANE Select	c.*434T>G		3_prime_UTR	Exon 6 of 6	ENSP00000466058.2	Q9NYR8
	RDH8	ENST00000651512.1		c.*434T>G		3_prime_UTR	Exon 6 of 6	ENSP00000498711.1	K7ELF7
	RDH8	ENST00000587782.1	TSL:2	c.*577T>G		downstream_gene	N/A	ENSP00000465773.1	K7EKT5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 17528 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 9016

African (AFR) AF: 0.00 AC: 0 AN: 418

American (AMR) AF: 0.00 AC: 0 AN: 2628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 354

East Asian (EAS) AF: 0.00 AC: 0 AN: 796

South Asian (SAS) AF: 0.00 AC: 0 AN: 1510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 24

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10502

Other (OTH) AF: 0.00 AC: 0 AN: 874

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 2151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.35
PhyloP100		0.33

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;