dbSNP rs7741: AKR1C3:p.Pro30Pro (chr10-5096415-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003739.6(AKR1C3):c.90G>A(p.Pro30Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,612,162 control chromosomes in the GnomAD database, including 96,429 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 0.32 ( 8461 hom., cov: 32)

Exomes 𝑓: 0.34 ( 87968 hom. )

Consequence

AKR1C3
NM_003739.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.54

Publications

20 publications found

Variant links:

Genes affected

AKR1C3 (HGNC:386): (aldo-keto reductase family 1 member C3) 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 reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

AKR1C3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

Synonymous conserved (PhyloP=-2.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C3	NM_003739.6 link	c.90G>A	p.Pro30Pro	synonymous_variant	Exon 2 of 9	ENST00000380554.5	NP_003730.4	P42330-1
AKR1C3	NM_001253908.2 link	c.90G>A	p.Pro30Pro	synonymous_variant	Exon 2 of 9		NP_001240837.1	P42330A0A0A0MSS8
AKR1C3	NM_001253909.2 link	c.90G>A	p.Pro30Pro	synonymous_variant	Exon 2 of 3		NP_001240838.1	B4DKT3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C3	ENST00000380554.5 link	c.90G>A	p.Pro30Pro	synonymous_variant	Exon 2 of 9	1	NM_003739.6	ENSP00000369927.3		P42330-1

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48941

AN:

151886

Hom.:

8454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.281

GnomAD2 exomes

AF:

0.280

AC:

70005

AN:

250292

AF XY:

0.279

show subpopulations

Gnomad AFR exome

AF:

0.333

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.00191

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.336

AC:

490762

AN:

1460158

Hom.:

87968

Cov.:

AF XY:

0.332

AC XY:

240913

AN XY:

726318

show subpopulations

African (AFR)

AF:

0.320

AC:

10671

AN:

33368

American (AMR)

AF:

0.172

AC:

7678

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6329

AN:

26040

East Asian (EAS)

AF:

0.00270

AC:

107

AN:

39674

South Asian (SAS)

AF:

0.184

AC:

15860

AN:

86054

European-Finnish (FIN)

AF:

0.405

AC:

21591

AN:

53340

Middle Eastern (MID)

AF:

0.186

AC:

1069

AN:

5752

European-Non Finnish (NFE)

AF:

0.368

AC:

408771

AN:

1110928

Other (OTH)

AF:

0.310

AC:

18686

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

17098

34197

51295

68394

85492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12658

25316

37974

50632

63290

<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:

0.322

AC:

48984

AN:

152004

Hom.:

8461

Cov.:

AF XY:

0.320

AC XY:

23813

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.329

AC:

13660

AN:

41472

American (AMR)

AF:

0.254

AC:

3881

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

824

AN:

3468

East Asian (EAS)

AF:

0.00328

AC:

AN:

5178

South Asian (SAS)

AF:

0.165

AC:

795

AN:

4816

European-Finnish (FIN)

AF:

0.405

AC:

4270

AN:

10552

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.362

AC:

24584

AN:

67938

Other (OTH)

AF:

0.278

AC:

586

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1647

3294

4941

6588

8235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.320

Hom.:

6775

Bravo

AF:

0.309

Asia WGS

AF:

0.0980

AC:

341

AN:

3478

EpiCase

AF:

0.347

EpiControl

AF:

0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.6

(source)

DANN

Benign

0.85

PhyloP100

-2.5

Mutation Taster

=300/0

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