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:):

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	UniProt
RDH12	NM_152443.3	c.-219-218A>G		intron_variant		ENST00000551171.6
GPHN	XM_047430879.1	c.1313-12989A>G		intron_variant
RDH12	XM_047430965.1	c.-219-218A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RDH12	ENST00000551171.6	c.-219-218A>G		intron_variant		1	NM_152443.3	P1
RDH12	ENST00000267502.3	c.-219-218A>G		intron_variant		5		P1

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;