Variant chr14-67727373-AG-A 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.658+187del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 623,976 control chromosomes in the GnomAD database, including 2,736 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.090 ( 629 hom., cov: 31)

Exomes 𝑓: 0.090 ( 2107 hom. )

Consequence

RDH12
NM_152443.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.266

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 -10 ACMG points.

BP6

Variant 14-67727373-AG-A is Benign according to our data. Variant chr14-67727373-AG-A is described in ClinVar as [Benign]. Clinvar id is 1182845.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
RDH12	NM_152443.3 linkuse as main transcript	c.658+187del	intron_variant	ENST00000551171.6
GPHN	XM_047430879.1 linkuse as main transcript	c.1313-7818del	intron_variant
RDH12	XM_047430965.1 linkuse as main transcript	c.658+187del	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
RDH12	ENST00000551171.6 linkuse as main transcript	c.658+187del	intron_variant		1	NM_152443.3	P1
RDH12	ENST00000267502.3 linkuse as main transcript	c.658+187del	intron_variant		5		P1
ZFYVE26	ENST00000394455.6 linkuse as main transcript	n.4134del	non_coding_transcript_exon_variant	15/15	2
RDH12	ENST00000552873.1 linkuse as main transcript	n.27+187del	intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0895

AC:

13615

AN:

152046

Hom.:

627

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0952

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0937

Gnomad ASJ

AF:

0.0992

Gnomad EAS

AF:

0.00501

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.0847

Gnomad OTH

AF:

0.119

GnomAD4 exome

AF:

0.0896

AC:

42271

AN:

471814

Hom.:

2107

Cov.:

AF XY:

0.0915

AC XY:

23007

AN XY:

251544

show subpopulations

Gnomad4 AFR exome

AF:

0.0990

Gnomad4 AMR exome

AF:

0.0861

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.00270

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.0885

Gnomad4 OTH exome

AF:

0.0989

GnomAD4 genome

AF:

0.0895

AC:

13619

AN:

152162

Hom.:

629

Cov.:

AF XY:

0.0912

AC XY:

6785

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0950

Gnomad4 AMR

AF:

0.0937

Gnomad4 ASJ

AF:

0.0992

Gnomad4 EAS

AF:

0.00502

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.0847

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.0944

Hom.:

Bravo

AF:

0.0870

Asia WGS

AF:

0.0590

AC:

205

AN:

3478

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

May 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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