19-55038944-A-G

Variant names:

• chr19-55038944-A-G
• rs1654433
• ENST00000585492.1:n.1001+5961T>C

Variant summary

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

The ENST00000585492.1(ENSG00000267149):​n.1001+5961T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,064 control chromosomes in the GnomAD database, including 50,699 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 0.81 (50699 hom., cov: 31)
• Consequence: ENSG00000267149 ENST00000585492.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

Genes affected

ENSG00000267149 (HGNC:):

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

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6-AS1	XR_001754012.3	n.122-3856A>G		intron_variant	Intron 2 of 2
GP6-AS1	XR_001754013.3	n.112-3856A>G		intron_variant	Intron 2 of 2
RDH13	XM_011526408.4	c.*3158T>C		downstream_gene_variant			XP_011524710.1
RDH13	XR_007066569.1	n.*159T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000267149	ENST00000585492.1	n.1001+5961T>C		intron_variant	Intron 5 of 5	2
GP6-AS1	ENST00000586845.1	n.134-3888A>G		intron_variant	Intron 2 of 2	3
GP6-AS1	ENST00000586961.1	n.45-3888A>G		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123612 AN: 151946 Hom.: 50673 Cov.: 31

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.813 AC: 123695 AN: 152064 Hom.: 50699 Cov.: 31 AF XY: 0.819 AC XY: 60852 AN XY: 74336

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.854

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.825

Alfa AF: 0.792 Hom.: 5973

Bravo AF: 0.805

Asia WGS AF: 0.884 AC: 3074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1654433; hg19: chr19-55550312;