rs1155931

chr10-5158884-C-T

Variant summary

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

The NM_001395972.1(AKR1C8):c.580-175G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,068 control chromosomes in the GnomAD database, including 22,129 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 0.53 (22129 hom., cov: 32)
• Consequence: AKR1C8 NM_001395972.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.67

Genes affected

AKR1C8 (HGNC:23469): (aldo-keto reductase family 1 member C8) Predicted to enable D-threo-aldose 1-dehydrogenase activity; aldo-keto reductase (NADP) activity; and estradiol 17-beta-dehydrogenase activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C8	NM_001395972.1	c.580-175G>A		intron_variant		ENST00000648824.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C8	ENST00000648824.2	c.580-175G>A		intron_variant			NM_001395972.1	P1
AKR1C8	ENST00000584929.7	c.*246-175G>A		intron_variant, NMD_transcript_variant
AKR1C8	ENST00000578467.2	n.718+999G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80121 AN: 151952 Hom.: 22120 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.527 AC: 80156 AN: 152068 Hom.: 22129 Cov.: 32 AF XY: 0.526 AC XY: 39115 AN XY: 74354

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.463

Alfa AF: 0.566 Hom.: 3111

Bravo AF: 0.509

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	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: rs1155931; hg19: chr10-5201082;