dbSNP rs41314625: AKR1C1:c.447+144G>A (chr10-4968530-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.44

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AKR1C1	NM_001353.6 link	c.447+144G>A		intron_variant	Intron 4 of 8	ENST00000380872.9	NP_001344.2	Q04828

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AKR1C1	ENST00000380872.9 link	c.447+144G>A	intron_variant	Intron 4 of 8	1	NM_001353.6	ENSP00000370254.4	Q04828
AKR1C1	ENST00000442997.5 link	c.345+144G>A	intron_variant	Intron 4 of 6	3		ENSP00000416415.1	H0Y804
AKR1C1	ENST00000380859.1 link	c.453+144G>A	intron_variant	Intron 4 of 5	3		ENSP00000370240.1	A6NHU4
AKR1C1	ENST00000477661.1 link	n.1904+144G>A	intron_variant	Intron 3 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.0938

AC:

14258

AN:

151958

Hom.:

834

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0575

AC:

1839

AN:

31976

American (AMR)

AF:

0.0484

AC:

1840

AN:

38018

Ashkenazi Jewish (ASJ)

AF:

0.0397

AC:

935

AN:

23548

East Asian (EAS)

AF:

0.000154

AC:

AN:

38868

South Asian (SAS)

AF:

0.0318

AC:

2508

AN:

78792

European-Finnish (FIN)

AF:

0.207

AC:

10570

AN:

50946

Middle Eastern (MID)

AF:

0.0513

AC:

281

AN:

5476

European-Non Finnish (NFE)

AF:

0.121

AC:

127872

AN:

1057896

Other (OTH)

AF:

0.0929

AC:

5339

AN:

57498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

6463

12926

19390

25853

32316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4486

8972

13458

17944

22430

<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:

0.0938

AC:

14262

AN:

152076

Hom.:

834

Cov.:

AF XY:

0.0957

AC XY:

7115

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0632

AC:

2621

AN:

41498

American (AMR)

AF:

0.0620

AC:

947

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0352

AC:

122

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5184

South Asian (SAS)

AF:

0.0270

AC:

130

AN:

4814

European-Finnish (FIN)

AF:

0.213

AC:

2253

AN:

10562

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7974

AN:

67958

Other (OTH)

AF:

0.0820

AC:

173

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

608

1216

1823

2431

3039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0513

Hom.:

Bravo

AF:

0.0815

Asia WGS

AF:

0.0160

AC:

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

(source)

DANN

Benign

0.58

PhyloP100

-1.4

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