dbSNP rs1138566: AKR1C1:p.Tyr5Tyr (chr10-4963459-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001353.6(AKR1C1):c.15T>C(p.Tyr5Tyr) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.438

Publications

2 publications found

Variant links:

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]

AKR1C1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.026).

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 rank	MANE	Protein	UniProt
AKR1C1	NM_001353.6 link	c.15T>C	p.Tyr5Tyr	synonymous_variant	Exon 1 of 9	ENST00000380872.9	NP_001344.2	Q04828

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AKR1C1	ENST00000380872.9 link	c.15T>C	p.Tyr5Tyr	synonymous_variant	Exon 1 of 9	1	NM_001353.6	ENSP00000370254.4	Q04828
AKR1C1	ENST00000442997.5 link	c.9T>C	p.Tyr3Tyr	synonymous_variant	Exon 1 of 7	3		ENSP00000416415.1	H0Y804
AKR1C1	ENST00000477661.1 link	n.207T>C		non_coding_transcript_exon_variant	Exon 1 of 8	5

Frequencies

GnomAD3 genomes

AF:

0.0536

AC:

8127

AN:

151652

Hom.:

756

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0145

AC:

3652

AN:

251364

AF XY:

0.0107

show subpopulations

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 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.:

AF XY:

0.00520

AC XY:

3781

AN XY:

726564

show subpopulations

African (AFR)

AF:

0.199

AC:

6644

AN:

33338

American (AMR)

AF:

0.00899

AC:

402

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.000536

AC:

AN:

26132

East Asian (EAS)

AF:

0.00297

AC:

118

AN:

39698

South Asian (SAS)

AF:

0.000557

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.0108

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000536

AC:

596

AN:

1110954

Other (OTH)

AF:

0.0123

AC:

740

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

314

629

943

1258

1572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

210

420

630

840

1050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0538

AC:

8166

AN:

151770

Hom.:

763

Cov.:

AF XY:

0.0525

AC XY:

3898

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.186

AC:

7705

AN:

41366

American (AMR)

AF:

0.0195

AC:

298

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00426

AC:

AN:

5170

South Asian (SAS)

AF:

0.000417

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000826

AC:

AN:

67804

Other (OTH)

AF:

0.0366

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

284

569

853

1138

1422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0134

Hom.:

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

(source)

DANN

Benign

0.72

PhyloP100

-0.44

PromoterAI

0.057

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over