Variant 19-10021730-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015725.4(RDH8):c.917C>T(p.Thr306Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000524 in 1,613,774 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 4 hom. )

Consequence

RDH8
NM_015725.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.209

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011547089).

BP6

Variant 19-10021730-C-T is Benign according to our data. Variant chr19-10021730-C-T is described in ClinVar as [Benign]. Clinvar id is 791350.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RDH8	NM_015725.4 linkuse as main transcript	c.917C>T	p.Thr306Met	missense_variant	6/6	ENST00000591589.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RDH8	ENST00000591589.3 linkuse as main transcript	c.917C>T	p.Thr306Met	missense_variant	6/6	1	NM_015725.4	P1
RDH8	ENST00000651512.1 linkuse as main transcript	c.977C>T	p.Thr326Met	missense_variant	6/6
RDH8	ENST00000587782.1 linkuse as main transcript	c.*124C>T		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

357

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00799

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000650

AC:

163

AN:

250858

Hom.:

AF XY:

0.000457

AC XY:

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.00887

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000333

AC:

486

AN:

1461438

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

228

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.00968

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000782

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.00236

AC:

359

AN:

152336

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00799

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000460

Hom.:

Bravo

AF:

0.00277

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000749

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.0

DANN

Benign

0.96

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.21

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.62

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

Sift4G

Benign

0.068

Vest4

0.26

MVP

0.28

MPC

0.35

ClinPred

0.016

GERP RS

-6.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over