rs1138566

chr10-4963459-T-C

Variant summary

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

The NM_001353.6(AKR1C1):c.15T>C(p.Tyr5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,612,282 control chromosomes in the GnomAD database, including 1,514 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 0.054 (763 hom., cov: 31)
  • Exomes 𝑓: 0.0059 (751 hom.)
• Consequence: AKR1C1 NM_001353.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C1	NM_001353.6	c.15T>C	p.Tyr5=	synonymous_variant	1/9	ENST00000380872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C1	ENST00000380872.9	c.15T>C	p.Tyr5=	synonymous_variant	1/9	1	NM_001353.6	P1
AKR1C1	ENST00000442997.5	c.12T>C	p.Tyr4=	synonymous_variant	1/7	3
AKR1C1	ENST00000477661.1	n.207T>C		non_coding_transcript_exon_variant	1/8	5

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8127 AN: 151652 Hom.: 756 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00425

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000826

Gnomad OTH AF: 0.0370

GnomAD3 exomes AF: 0.0145 AC: 3652 AN: 251364 Hom.: 330 AF XY: 0.0107 AC XY: 1452 AN XY: 135854

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.00839

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00440

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000792

Gnomad OTH exome AF: 0.00685

GnomAD4 exome AF: 0.00591 AC: 8625 AN: 1460512 Hom.: 751 Cov.: 31 AF XY: 0.00520 AC XY: 3781 AN XY: 726564

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.00899

Gnomad4 ASJ exome AF: 0.000536

Gnomad4 EAS exome AF: 0.00297

Gnomad4 SAS exome AF: 0.000557

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000536

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.0538 AC: 8166 AN: 151770 Hom.: 763 Cov.: 31 AF XY: 0.0525 AC XY: 3898 AN XY: 74220

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0195

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00426

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000826

Gnomad4 OTH AF: 0.0366

Alfa AF: 0.0134 Hom.: 51

Bravo AF: 0.0620

EpiCase AF: 0.00126

EpiControl AF: 0.00101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.7
Dann	Benign	0.72

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: rs1138566; hg19: chr10-5005651;