14-67722206-A-G

Position:

• chr14-67722206-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152443.3(RDH12):​c.-219-218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 152,108 control chromosomes in the GnomAD database, including 853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.089 (853 hom., cov: 32)
• Consequence: RDH12 NM_152443.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.239

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 14-67722206-A-G is Benign according to our data. Variant chr14-67722206-A-G is described in ClinVar as [Benign]. Clinvar id is 1231282.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RDH12	NM_152443.3	c.-219-218A>G		intron_variant		ENST00000551171.6	NP_689656.2
GPHN	XM_047430879.1	c.1313-12989A>G		intron_variant			XP_047286835.1
RDH12	XM_047430965.1	c.-219-218A>G		intron_variant			XP_047286921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RDH12	ENST00000551171.6	c.-219-218A>G		intron_variant		1	NM_152443.3	ENSP00000449079.1
RDH12	ENST00000267502.3	c.-219-218A>G		intron_variant		5		ENSP00000267502.3

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13494 AN: 151990 Hom.: 851 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.0956

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0845

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

GnomAD4 genome AF: 0.0890 AC: 13537 AN: 152108 Hom.: 853 Cov.: 32 AF XY: 0.0890 AC XY: 6618 AN XY: 74362

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.0967

Gnomad4 FIN AF: 0.0240

Gnomad4 NFE AF: 0.0425

Gnomad4 OTH AF: 0.0860

Alfa AF: 0.0596 Hom.: 217

Bravo AF: 0.104

Asia WGS AF: 0.163 AC: 564 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.91
DANN	Benign	0.62

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: rs910315; hg19: chr14-68188923;