rs41314625

Positions:

• chr10-4968530-G-A
• chr10-4968530-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.447+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,535,094 control chromosomes in the GnomAD database, including 12,006 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 0.094 (834 hom., cov: 31)
  • Exomes 𝑓: 0.11 (11172 hom.)
• Consequence: AKR1C1 NM_001353.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C1	NM_001353.6	c.447+144G>A		intron_variant		ENST00000380872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C1	ENST00000380872.9	c.447+144G>A		intron_variant		1	NM_001353.6	P1
AKR1C1	ENST00000380859.1	c.453+144G>A		intron_variant		3
AKR1C1	ENST00000442997.5	c.347+144G>A		intron_variant		3
AKR1C1	ENST00000477661.1	n.1904+144G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14258 AN: 151958 Hom.: 834 Cov.: 31

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0266

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0829

GnomAD4 exome AF: 0.109 AC: 151190 AN: 1383018 Hom.: 11172 AF XY: 0.107 AC XY: 73263 AN XY: 684374

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.0484

Gnomad4 ASJ exome AF: 0.0397

Gnomad4 EAS exome AF: 0.000154

Gnomad4 SAS exome AF: 0.0318

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.0929

GnomAD4 genome AF: 0.0938 AC: 14262 AN: 152076 Hom.: 834 Cov.: 31 AF XY: 0.0957 AC XY: 7115 AN XY: 74334

Gnomad4 AFR AF: 0.0632

Gnomad4 AMR AF: 0.0620

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0270

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.0820

Alfa AF: 0.0513 Hom.: 64

Bravo AF: 0.0815

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.57
DANN	Benign	0.58

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: rs41314625; hg19: chr10-5010722;