Genetic Variant 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AKR1C1	NM_001353.6	MANE Select	c.447+144G>A		intron	N/A	NP_001344.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKR1C1	ENST00000380872.9	TSL:1 MANE Select	c.447+144G>A	intron	N/A	ENSP00000370254.4	Q04828
AKR1C1	ENST00000970520.1		c.447+144G>A	intron	N/A	ENSP00000640579.1
AKR1C1	ENST00000859341.1		c.370-292G>A	intron	N/A	ENSP00000529400.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over