rs1781930

Positions:

• chr10-5154078-G-A
• chr10-5154078-G-C

Variant summary

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

The NM_001395972.1(AKR1C8):​c.*62C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 451,612 control chromosomes in the GnomAD database, including 5,360 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 0.13 (1513 hom., cov: 32)
  • Exomes 𝑓: 0.15 (3847 hom.)
• Consequence: AKR1C8 NM_001395972.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C8	NM_001395972.1	c.*62C>T		3_prime_UTR_variant	9/9	ENST00000648824.2	NP_001382901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C8	ENST00000648824.2	c.*62C>T		3_prime_UTR_variant	9/9		NM_001395972.1	ENSP00000496804	P1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19454 AN: 151956 Hom.: 1510 Cov.: 32

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.153 AC: 45924 AN: 299538 Hom.: 3847 AF XY: 0.150 AC XY: 25533 AN XY: 169814

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.128 AC: 19457 AN: 152074 Hom.: 1513 Cov.: 32 AF XY: 0.130 AC XY: 9650 AN XY: 74342

Gnomad4 AFR AF: 0.0372

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.107

Alfa AF: 0.161 Hom.: 3448

Bravo AF: 0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1781930; hg19: chr10-5196273;