19-55051034-A-G

Position:

• chr19-55051034-A-G

Variant summary

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

The NM_001145971.2(RDH13):​c.341-2271T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 149,068 control chromosomes in the GnomAD database, including 14,341 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 0.43 (14341 hom., cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RDH13 NM_001145971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

Genes affected

RDH13 (HGNC:19978): (retinol dehydrogenase 13) This gene encodes a mitochondrial short-chain dehydrogenase/reductase, which catalyzes the reduction and oxidation of retinoids. The encoded enzyme may function in retinoic acid production and may also protect the mitochondria against oxidative stress. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

ENSG00000267149 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RDH13	NM_001145971.2	c.341-2271T>C		intron_variant		ENST00000415061.8	NP_001139443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RDH13	ENST00000415061.8	c.341-2271T>C		intron_variant		1	NM_001145971.2	ENSP00000391121.2

Frequencies

GnomAD3 genomes AF: 0.429 AC: 63880 AN: 148972 Hom.: 14346 Cov.: 27

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.443

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.429 AC: 63881 AN: 149068 Hom.: 14341 Cov.: 27 AF XY: 0.428 AC XY: 30939 AN XY: 72252

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.444

Alfa AF: 0.465 Hom.: 8968

Bravo AF: 0.418

Asia WGS AF: 0.432 AC: 1503 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.64

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: rs6509916; hg19: chr19-55562402;