dbSNP rs9329316: AKR1C3:c.930-350T>C (chr10-5107111-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_003739.6(AKR1C3):c.930-350T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,052 control chromosomes in the GnomAD database, including 5,580 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 0.26 ( 5580 hom., cov: 32)

Consequence

AKR1C3
NM_003739.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0990

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 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.930-350T>C		intron	N/A	NP_003730.4
	AKR1C3	NM_001253908.2		c.930-350T>C		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.930-350T>C	intron	N/A	ENSP00000369927.3	P42330-1
AKR1C3	ENST00000439082.7	TSL:5	c.930-350T>C	intron	N/A	ENSP00000401327.3	A0A0A0MSS8
AKR1C3	ENST00000879767.1		c.930-359T>C	intron	N/A	ENSP00000549826.1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40058

AN:

151938

Hom.:

5551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.264

AC:

40122

AN:

152052

Hom.:

5580

Cov.:

AF XY:

0.261

AC XY:

19396

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.333

AC:

13817

AN:

41458

American (AMR)

AF:

0.236

AC:

3612

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

916

AN:

3470

East Asian (EAS)

AF:

0.231

AC:

1197

AN:

5172

South Asian (SAS)

AF:

0.213

AC:

1030

AN:

4826

European-Finnish (FIN)

AF:

0.223

AC:

2356

AN:

10564

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.237

AC:

16128

AN:

67964

Other (OTH)

AF:

0.306

AC:

645

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1476

2951

4427

5902

7378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.256

Hom.:

701

Bravo

AF:

0.270

Asia WGS

AF:

0.256

AC:

883

AN:

3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.9

(source)

DANN

Benign

0.68

PhyloP100

0.099

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over