rs1138576

chr10-4965985-T-Achr10-4965985-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001353.6(AKR1C1):c.156T>A(p.Ala52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,614,188 control chromosomes in the GnomAD database, including 4 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 0.00080 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: AKR1C1 NM_001353.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-2.98 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C1	NM_001353.6	c.156T>A	p.Ala52=	synonymous_variant	2/9	ENST00000380872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C1	ENST00000380872.9	c.156T>A	p.Ala52=	synonymous_variant	2/9	1	NM_001353.6	P1

Frequencies

GnomAD3 genomes AF: 0.000801 AC: 122 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000899 AC: 226 AN: 251404 Hom.: 1 AF XY: 0.000876 AC XY: 119 AN XY: 135868

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00185

Gnomad NFE exome AF: 0.00156

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.00118 AC: 1728 AN: 1461844 Hom.: 4 Cov.: 31 AF XY: 0.00110 AC XY: 802 AN XY: 727216

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00227

Gnomad4 NFE exome AF: 0.00139

Gnomad4 OTH exome AF: 0.000695

GnomAD4 genome AF: 0.000801 AC: 122 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.000832 AC XY: 62 AN XY: 74500

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.00137

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000892 Hom.: 0

Bravo AF: 0.000729

EpiCase AF: 0.000654

EpiControl AF: 0.00130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.0
Dann	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1138576; hg19: chr10-5008177;