rs12882315

Positions:

• chr14-67705011-C-A
• chr14-67705011-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152443.3(RDH12):​c.-275+3076C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,144 control chromosomes in the GnomAD database, including 1,477 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1477 hom., cov: 32)
• Consequence: RDH12 NM_152443.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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]

GPHN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RDH12	NM_152443.3	c.-275+3076C>A		intron_variant		ENST00000551171.6
GPHN	XM_047430879.1	c.1313-30184C>A		intron_variant
RDH12	XM_047430965.1	c.-309+3076C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RDH12	ENST00000551171.6	c.-275+3076C>A		intron_variant		1	NM_152443.3	P1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19203 AN: 152026 Hom.: 1481 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.135

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.126 AC: 19201 AN: 152144 Hom.: 1477 Cov.: 32 AF XY: 0.134 AC XY: 9939 AN XY: 74346

Gnomad4 AFR AF: 0.0830

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.136

Alfa AF: 0.113 Hom.: 175

Bravo AF: 0.123

Asia WGS AF: 0.268 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.97
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs12882315; hg19: chr14-68171728;