Genetic Variant RDH8:c.*434T>A (chr19-10022183-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.333

Publications

6 publications found

Variant links:

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]

RDH8 links:

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ACMG classification

Classification was made for transcript

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.

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>A		3_prime_UTR	Exon 6 of 6	NP_056540.3	Q9NYR8

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79048

AN:

151598

Hom.:

21070

Cov.:

show subpopulations

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.:

AF XY:

0.445

AC XY:

3993

AN XY:

8970

show subpopulations

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:

AN:

European-Non Finnish (NFE)

AF:

0.391

AC:

4085

AN:

10448

Other (OTH)

AF:

0.434

AC:

375

AN:

864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

191

381

572

762

953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.522

AC:

79138

AN:

151716

Hom.:

21099

Cov.:

AF XY:

0.528

AC XY:

39146

AN XY:

74130

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1917

3834

5751

7668

9585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

688

1376

2064

2752

3440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.5

(source)

DANN

Benign

0.77

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over