Genetic Variant NM_001353.6:c.369+129T>C (chr10-4967172-T-C) – 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.369+129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,097,164 control chromosomes in the GnomAD database, including 251,262 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 0.69 ( 36500 hom., cov: 33)

Exomes 𝑓: 0.67 ( 214762 hom. )

Consequence

AKR1C1
NM_001353.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0640

Publications

8 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C1	NM_001353.6 link	c.369+129T>C		intron_variant	Intron 3 of 8	ENST00000380872.9	NP_001344.2	Q04828

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C1	ENST00000380872.9 link	c.369+129T>C		intron_variant	Intron 3 of 8	1	NM_001353.6	ENSP00000370254.4		Q04828

Frequencies

GnomAD3 genomes

AF:

0.691

AC:

104966

AN:

151970

Hom.:

36469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.721

Gnomad AMI

AF:

0.641

Gnomad AMR

AF:

0.715

Gnomad ASJ

AF:

0.673

Gnomad EAS

AF:

0.802

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.772

Gnomad MID

AF:

0.688

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.706

GnomAD4 exome

AF:

0.671

AC:

634581

AN:

945078

Hom.:

214762

Cov.:

AF XY:

0.670

AC XY:

321156

AN XY:

479358

show subpopulations

African (AFR)

AF:

0.739

AC:

16307

AN:

22072

American (AMR)

AF:

0.772

AC:

18884

AN:

24452

Ashkenazi Jewish (ASJ)

AF:

0.690

AC:

12519

AN:

18146

East Asian (EAS)

AF:

0.817

AC:

27529

AN:

33702

South Asian (SAS)

AF:

0.653

AC:

37821

AN:

57950

European-Finnish (FIN)

AF:

0.777

AC:

36857

AN:

47432

Middle Eastern (MID)

AF:

0.684

AC:

3120

AN:

4564

European-Non Finnish (NFE)

AF:

0.652

AC:

453008

AN:

694356

Other (OTH)

AF:

0.673

AC:

28536

AN:

42404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

9565

19131

28696

38262

47827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10242

20484

30726

40968

51210

<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:

0.691

AC:

105044

AN:

152086

Hom.:

36500

Cov.:

AF XY:

0.695

AC XY:

51641

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.721

AC:

29890

AN:

41454

American (AMR)

AF:

0.715

AC:

10940

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.673

AC:

2338

AN:

3472

East Asian (EAS)

AF:

0.802

AC:

4156

AN:

5184

South Asian (SAS)

AF:

0.621

AC:

2986

AN:

4812

European-Finnish (FIN)

AF:

0.772

AC:

8148

AN:

10560

Middle Eastern (MID)

AF:

0.682

AC:

199

AN:

292

European-Non Finnish (NFE)

AF:

0.652

AC:

44302

AN:

67988

Other (OTH)

AF:

0.710

AC:

1502

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1678

3356

5035

6713

8391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<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:

0.668

Hom.:

128327

Bravo

AF:

0.694

Asia WGS

AF:

0.745

AC:

2590

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.73

(source)

DANN

Benign

0.61

PhyloP100

0.064

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