rs1155931

Variant names:

• chr10-5158884-C-T
• rs1155931
• NM_001395972.1:c.580-175G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AKR1C8	NM_001395972.1	c.580-175G>A		intron_variant	Intron 5 of 8	ENST00000648824.2	NP_001382901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C8	ENST00000648824.2	c.580-175G>A		intron_variant	Intron 5 of 8		NM_001395972.1	ENSP00000496804.1
AKR1C8	ENST00000578467.2	n.718+999G>A		intron_variant	Intron 6 of 7	2
AKR1C8	ENST00000584929.7	n.*246-175G>A		intron_variant	Intron 6 of 9	6		ENSP00000496857.1

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

African (AFR) AF: 0.469 AC: 19442 AN: 41440

American (AMR) AF: 0.493 AC: 7522 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3470

East Asian (EAS) AF: 0.141 AC: 728 AN: 5170

South Asian (SAS) AF: 0.354 AC: 1709 AN: 4824

European-Finnish (FIN) AF: 0.671 AC: 7101 AN: 10590

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40740 AN: 67988

Other (OTH) AF: 0.463 AC: 979 AN: 2114

Alfa AF: 0.562 Hom.: 3198

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
PhyloP100		-3.7

Splicing

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

Other links and lift over

dbSNP: rs1155931; hg19: chr10-5201082;