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:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]

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	Protein	UniProt
RDH12	NM_152443.3	c.-275+3076C>A		intron_variant		ENST00000551171.6	NP_689656.2
GPHN	XM_047430879.1	c.1313-30184C>A		intron_variant			XP_047286835.1
RDH12	XM_047430965.1	c.-309+3076C>A		intron_variant			XP_047286921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RDH12	ENST00000551171.6	c.-275+3076C>A		intron_variant		1	NM_152443.3	ENSP00000449079.1

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;