dbSNP rs2275928: AKR1C3:c.929+40G>A (chr10-5105717-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_003739.6(AKR1C3):c.929+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,515,468 control chromosomes in the GnomAD database, including 255,408 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 0.58 ( 26266 hom., cov: 31)

Exomes 𝑓: 0.57 ( 229142 hom. )

Consequence

AKR1C3
NM_003739.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.786

Publications

14 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003739.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003739.6. 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
	AKR1C3	NM_003739.6	MANE Select	c.929+40G>A		intron	N/A	NP_003730.4
	AKR1C3	NM_001253908.2		c.929+40G>A		intron	N/A	NP_001240837.1	A0A0A0MSS8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKR1C3	ENST00000380554.5	TSL:1 MANE Select	c.929+40G>A	intron	N/A	ENSP00000369927.3	P42330-1
AKR1C3	ENST00000439082.7	TSL:5	c.929+40G>A	intron	N/A	ENSP00000401327.3	A0A0A0MSS8
AKR1C3	ENST00000879767.1		c.929+40G>A	intron	N/A	ENSP00000549826.1

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88141

AN:

151944

Hom.:

26230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.639

Gnomad AMI

AF:

0.690

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.599

Gnomad OTH

AF:

0.577

GnomAD2 exomes

AF:

0.519

AC:

117209

AN:

225638

AF XY:

0.519

show subpopulations

Gnomad AFR exome

AF:

0.646

Gnomad AMR exome

AF:

0.355

Gnomad ASJ exome

AF:

0.502

Gnomad EAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.651

Gnomad NFE exome

AF:

0.603

Gnomad OTH exome

AF:

0.563

GnomAD4 exome

AF:

0.571

AC:

778970

AN:

1363406

Hom.:

229142

Cov.:

AF XY:

0.567

AC XY:

386751

AN XY:

681820

show subpopulations

African (AFR)

AF:

0.639

AC:

20123

AN:

31512

American (AMR)

AF:

0.367

AC:

15533

AN:

42294

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

12951

AN:

25410

East Asian (EAS)

AF:

0.200

AC:

7770

AN:

38930

South Asian (SAS)

AF:

0.417

AC:

34409

AN:

82598

European-Finnish (FIN)

AF:

0.638

AC:

33474

AN:

52454

Middle Eastern (MID)

AF:

0.570

AC:

3157

AN:

5536

European-Non Finnish (NFE)

AF:

0.603

AC:

619355

AN:

1027736

Other (OTH)

AF:

0.566

AC:

32198

AN:

56936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

15315

30630

45944

61259

76574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16210

32420

48630

64840

81050

<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:

0.580

AC:

88229

AN:

152062

Hom.:

26266

Cov.:

AF XY:

0.575

AC XY:

42734

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.639

AC:

26498

AN:

41460

American (AMR)

AF:

0.490

AC:

7501

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

1738

AN:

3470

East Asian (EAS)

AF:

0.235

AC:

1217

AN:

5182

South Asian (SAS)

AF:

0.395

AC:

1906

AN:

4820

European-Finnish (FIN)

AF:

0.629

AC:

6636

AN:

10554

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.599

AC:

40725

AN:

67970

Other (OTH)

AF:

0.579

AC:

1219

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1869

3739

5608

7478

9347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.589

Hom.:

36447

Bravo

AF:

0.572

Asia WGS

AF:

0.364

AC:

1264

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.30

(source)

DANN

Benign

0.15

PhyloP100

-0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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