19-55051034-A-G

Variant names:

• chr19-55051034-A-G
• rs6509916
• NM_001145971.2:c.341-2271T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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:):

GP6-AS1 (HGNC:55305): (GP6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH13	NM_001145971.2	MANE Select	c.341-2271T>C		intron	N/A	NP_001139443.1
	RDH13	NM_138412.4		c.128-2271T>C		intron	N/A	NP_612421.1
	RDH13	NR_027381.2		n.457-2271T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDH13	ENST00000415061.8	TSL:1 MANE Select	c.341-2271T>C		intron	N/A	ENSP00000391121.2
	RDH13	ENST00000396247.7	TSL:1	c.128-2271T>C		intron	N/A	ENSP00000379547.2
	RDH13	ENST00000610356.4	TSL:1	c.128-2271T>C		intron	N/A	ENSP00000477732.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.320 AC: 12946 AN: 40456

American (AMR) AF: 0.385 AC: 5740 AN: 14920

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1319 AN: 3464

East Asian (EAS) AF: 0.577 AC: 2901 AN: 5030

South Asian (SAS) AF: 0.404 AC: 1920 AN: 4754

European-Finnish (FIN) AF: 0.486 AC: 4585 AN: 9428

Middle Eastern (MID) AF: 0.448 AC: 130 AN: 290

European-Non Finnish (NFE) AF: 0.487 AC: 32972 AN: 67742

Other (OTH) AF: 0.444 AC: 920 AN: 2074

Alfa AF: 0.464 Hom.: 12635

Bravo AF: 0.418

Asia WGS AF: 0.432 AC: 1503 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.64
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6509916; hg19: chr19-55562402;