Variant 14-67722491-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_152443.3(RDH12):c.-152A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00734 in 771,534 control chromosomes in the GnomAD database, including 228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0079 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 190 hom. )

Consequence

RDH12
NM_152443.3 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.185

Variant links:

Genes affected

RDH12 (HGNC:19977): (retinol dehydrogenase 12) The protein encoded by this gene is an NADPH-dependent retinal reductase whose highest activity is toward 9-cis and all-trans-retinol. The encoded enzyme also plays a role in the metabolism of short-chain aldehydes but does not exhibit steroid dehydrogenase activity. Defects in this gene are a cause of Leber congenital amaurosis type 13 and Retinitis Pigmentosa 53. [provided by RefSeq, Sep 2015]

RDH12 links:

GPHN (HGNC:):

GPHN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 14-67722491-A-G is Benign according to our data. Variant chr14-67722491-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 313835.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
RDH12	NM_152443.3 linkuse as main transcript	c.-152A>G	5_prime_UTR_variant	3/9	ENST00000551171.6
RDH12	XM_047430965.1 linkuse as main transcript	c.-152A>G	5_prime_UTR_variant	3/9
GPHN	XM_047430879.1 linkuse as main transcript	c.1313-12704A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RDH12	ENST00000551171.6 linkuse as main transcript	c.-152A>G		5_prime_UTR_variant	3/9	1	NM_152443.3	P1
RDH12	ENST00000267502.3 linkuse as main transcript	c.-152A>G		5_prime_UTR_variant	2/8	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00788

AC:

1200

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0120

GnomAD4 exome

AF:

0.00721

AC:

4465

AN:

619216

Hom.:

190

Cov.:

AF XY:

0.00674

AC XY:

2271

AN XY:

336918

show subpopulations

Gnomad4 AFR exome

AF:

0.0144

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00151

Gnomad4 EAS exome

AF:

0.0908

Gnomad4 SAS exome

AF:

0.00397

Gnomad4 FIN exome

AF:

0.000992

Gnomad4 NFE exome

AF:

0.000460

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.00788

AC:

1201

AN:

152318

Hom.:

Cov.:

AF XY:

0.00811

AC XY:

604

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0134

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00901

Asia WGS

AF:

0.0540

AC:

189

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinitis Pigmentosa, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.3

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -17

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