Variant rs12387 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003739.6(AKR1C3):c.312G>A(p.Lys104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,613,590 control chromosomes in the GnomAD database, including 557,957 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 0.84 ( 54218 hom., cov: 31)

Exomes 𝑓: 0.83 ( 503739 hom. )

Consequence

AKR1C3
NM_003739.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.898

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

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP7

Synonymous conserved (PhyloP=-0.898 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AKR1C3	NM_003739.6 linkuse as main transcript	c.312G>A	p.Lys104=	synonymous_variant	3/9	ENST00000380554.5
AKR1C3	NM_001253908.2 linkuse as main transcript	c.312G>A	p.Lys104=	synonymous_variant	3/9
AKR1C3	NM_001253909.2 linkuse as main transcript	c.312G>A	p.Lys104=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000380554.5 linkuse as main transcript	c.312G>A	p.Lys104=	synonymous_variant	3/9	1	NM_003739.6	P4	P42330-1

Frequencies

GnomAD3 genomes

AF:

0.844

AC:

128299

AN:

151984

Hom.:

54167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.871

Gnomad AMI

AF:

0.880

Gnomad AMR

AF:

0.817

Gnomad ASJ

AF:

0.888

Gnomad EAS

AF:

0.867

Gnomad SAS

AF:

0.846

Gnomad FIN

AF:

0.828

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.831

Gnomad OTH

AF:

0.876

GnomAD3 exomes

AF:

0.836

AC:

210169

AN:

251356

Hom.:

88011

AF XY:

0.837

AC XY:

113756

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.874

Gnomad AMR exome

AF:

0.800

Gnomad ASJ exome

AF:

0.888

Gnomad EAS exome

AF:

0.865

Gnomad SAS exome

AF:

0.853

Gnomad FIN exome

AF:

0.836

Gnomad NFE exome

AF:

0.828

Gnomad OTH exome

AF:

0.838

GnomAD4 exome

AF:

0.830

AC:

1212755

AN:

1461490

Hom.:

503739

Cov.:

AF XY:

0.831

AC XY:

604304

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.874

Gnomad4 AMR exome

AF:

0.796

Gnomad4 ASJ exome

AF:

0.892

Gnomad4 EAS exome

AF:

0.884

Gnomad4 SAS exome

AF:

0.854

Gnomad4 FIN exome

AF:

0.830

Gnomad4 NFE exome

AF:

0.824

Gnomad4 OTH exome

AF:

0.840

GnomAD4 genome

AF:

0.844

AC:

128405

AN:

152100

Hom.:

54218

Cov.:

AF XY:

0.843

AC XY:

62679

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.871

Gnomad4 AMR

AF:

0.816

Gnomad4 ASJ

AF:

0.888

Gnomad4 EAS

AF:

0.868

Gnomad4 SAS

AF:

0.846

Gnomad4 FIN

AF:

0.828

Gnomad4 NFE

AF:

0.831

Gnomad4 OTH

AF:

0.877

Alfa

AF:

0.839

Hom.:

50661

Bravo

AF:

0.845

Asia WGS

AF:

0.862

AC:

2998

AN:

3478

EpiCase

AF:

0.839

EpiControl

AF:

0.835

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.31

DANN

Benign

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over