rs8483

chr10-4977767-G-Achr10-4977767-G-T

Variant summary

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

The NM_001353.6(AKR1C1):c.*25G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,590,706 control chromosomes in the GnomAD database, including 132,294 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 0.47 (17510 hom., cov: 29)
  • Exomes 𝑓: 0.40 (114784 hom.)
• Consequence: AKR1C1 NM_001353.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

Genes affected

AKR1C1 (HGNC:384): (aldo-keto reductase family 1 member C1) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reaction of progesterone to the inactive form 20-alpha-hydroxy-progesterone. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C1	NM_001353.6	c.*25G>A		3_prime_UTR_variant	9/9	ENST00000380872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C1	ENST00000380872.9	c.*25G>A		3_prime_UTR_variant	9/9	1	NM_001353.6	P1
AKR1C1	ENST00000477661.1	n.2454G>A		non_coding_transcript_exon_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.469 AC: 70998 AN: 151344 Hom.: 17475 Cov.: 29

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.460

GnomAD3 exomes AF: 0.452 AC: 110853 AN: 245420 Hom.: 26063 AF XY: 0.440 AC XY: 58535 AN XY: 132932

Gnomad AFR exome AF: 0.609

Gnomad AMR exome AF: 0.601

Gnomad ASJ exome AF: 0.311

Gnomad EAS exome AF: 0.554

Gnomad SAS exome AF: 0.405

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.395 AC: 568539 AN: 1439242 Hom.: 114784 Cov.: 27 AF XY: 0.393 AC XY: 282019 AN XY: 717112

Gnomad4 AFR exome AF: 0.611

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.580

Gnomad4 SAS exome AF: 0.408

Gnomad4 FIN exome AF: 0.548

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.469 AC: 71085 AN: 151464 Hom.: 17510 Cov.: 29 AF XY: 0.477 AC XY: 35310 AN XY: 73956

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.462

Alfa AF: 0.308 Hom.: 1208

Bravo AF: 0.478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.18
Dann	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs8483; hg19: chr10-5019959; COSMIC: COSV66513764;