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GeneBe

19-10018879-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_015725.4(RDH8):c.411C>T(p.Ile137=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,612,906 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 50 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 56 hom. )

Consequence

RDH8
NM_015725.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.741
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-10018879-C-T is Benign according to our data. Variant chr19-10018879-C-T is described in ClinVar as [Benign]. Clinvar id is 783822.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.741 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0145 (2214/152264) while in subpopulation AFR AF= 0.0504 (2092/41542). AF 95% confidence interval is 0.0486. There are 50 homozygotes in gnomad4. There are 1058 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 50 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RDH8NM_015725.4 linkuse as main transcriptc.411C>T p.Ile137= synonymous_variant 3/6 ENST00000591589.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RDH8ENST00000591589.3 linkuse as main transcriptc.411C>T p.Ile137= synonymous_variant 3/61 NM_015725.4 P1
RDH8ENST00000651512.1 linkuse as main transcriptc.471C>T p.Ile157= synonymous_variant 3/6
RDH8ENST00000589570.1 linkuse as main transcriptn.50+1664C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0145
AC:
2206
AN:
152146
Hom.:
50
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0503
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00544
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.00812
GnomAD3 exomes
AF:
0.00379
AC:
949
AN:
250502
Hom.:
25
AF XY:
0.00260
AC XY:
352
AN XY:
135362
show subpopulations
Gnomad AFR exome
AF:
0.0515
Gnomad AMR exome
AF:
0.00274
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000657
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000882
Gnomad OTH exome
AF:
0.00115
GnomAD4 exome
AF:
0.00147
AC:
2147
AN:
1460642
Hom.:
56
Cov.:
31
AF XY:
0.00126
AC XY:
912
AN XY:
726542
show subpopulations
Gnomad4 AFR exome
AF:
0.0515
Gnomad4 AMR exome
AF:
0.00251
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000813
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000900
Gnomad4 OTH exome
AF:
0.00318
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0145
AC:
2214
AN:
152264
Hom.:
50
Cov.:
32
AF XY:
0.0142
AC XY:
1058
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0504
Gnomad4 AMR
AF:
0.00543
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00803
Alfa
AF:
0.00707
Hom.:
20
Bravo
AF:
0.0167
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

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 submitterclinical testingInvitaeJul 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.29
Cadd
Benign
3.1
Dann
Benign
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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.

Other links and lift over

dbSNP: rs2233795; hg19: chr19-10129555; COSMIC: COSV50674991; COSMIC: COSV50674991; API