Variant 14-67727476-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_152443.3(RDH12):c.658+286G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 298,896 control chromosomes in the GnomAD database, including 34,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.54 ( 22581 hom., cov: 28)

Exomes 𝑓: 0.48 ( 12365 hom. )

Consequence

RDH12
NM_152443.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.298

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:

ZFYVE26 (HGNC:20761): (zinc finger FYVE-type containing 26) This gene encodes a protein which contains a FYVE zinc finger binding domain. The presence of this domain is thought to target these proteins to membrane lipids through interaction with phospholipids in the membrane. Mutations in this gene are associated with autosomal recessive spastic paraplegia-15. [provided by RefSeq, Oct 2008]

ZFYVE26 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 14-67727476-G-T is Benign according to our data. Variant chr14-67727476-G-T is described in ClinVar as [Benign]. Clinvar id is 1289717.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
RDH12	NM_152443.3 linkuse as main transcript	c.658+286G>T	intron_variant	ENST00000551171.6
GPHN	XM_047430879.1 linkuse as main transcript	c.1313-7719G>T	intron_variant
RDH12	XM_047430965.1 linkuse as main transcript	c.658+286G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
RDH12	ENST00000551171.6 linkuse as main transcript	c.658+286G>T	intron_variant		1	NM_152443.3	P1
RDH12	ENST00000267502.3 linkuse as main transcript	c.658+286G>T	intron_variant		5		P1
ZFYVE26	ENST00000394455.6 linkuse as main transcript	n.4032C>A	non_coding_transcript_exon_variant	15/15	2
RDH12	ENST00000552873.1 linkuse as main transcript	n.27+286G>T	intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.539

AC:

79034

AN:

146698

Hom.:

22573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.785

Gnomad AMR

AF:

0.550

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.429

Gnomad NFE

AF:

0.651

Gnomad OTH

AF:

0.511

GnomAD4 exome

AF:

0.478

AC:

72687

AN:

152118

Hom.:

12365

Cov.:

AF XY:

0.467

AC XY:

38572

AN XY:

82592

show subpopulations

Gnomad4 AFR exome

AF:

0.279

Gnomad4 AMR exome

AF:

0.433

Gnomad4 ASJ exome

AF:

0.466

Gnomad4 EAS exome

AF:

0.439

Gnomad4 SAS exome

AF:

0.385

Gnomad4 FIN exome

AF:

0.474

Gnomad4 NFE exome

AF:

0.523

Gnomad4 OTH exome

AF:

0.463

GnomAD4 genome

AF:

0.539

AC:

79072

AN:

146778

Hom.:

22581

Cov.:

AF XY:

0.533

AC XY:

38017

AN XY:

71364

show subpopulations

Gnomad4 AFR

AF:

0.342

Gnomad4 AMR

AF:

0.550

Gnomad4 ASJ

AF:

0.596

Gnomad4 EAS

AF:

0.551

Gnomad4 SAS

AF:

0.437

Gnomad4 FIN

AF:

0.568

Gnomad4 NFE

AF:

0.651

Gnomad4 OTH

AF:

0.508

Alfa

AF:

0.153

Hom.:

442

Bravo

AF:

0.529

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

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.29

DANN

Benign

0.55

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