Variant rs2275928 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C3	NM_003739.6 linkuse as main transcript	c.929+40G>A		intron_variant		ENST00000380554.5
AKR1C3	NM_001253908.2 linkuse as main transcript	c.929+40G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
AKR1C3	ENST00000380554.5 linkuse as main transcript	c.929+40G>A	intron_variant	1	NM_003739.6	P4	P42330-1
AKR1C3	ENST00000439082.7 linkuse as main transcript	c.929+40G>A	intron_variant	5		A1
AKR1C3	ENST00000605149.5 linkuse as main transcript	c.860+40G>A	intron_variant	2
AKR1C3	ENST00000603484.1 linkuse as main transcript	n.403+40G>A	intron_variant, non_coding_transcript_variant	2

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

GnomAD3 exomes

AF:

0.519

AC:

117209

AN:

225638

Hom.:

32339

AF XY:

0.519

AC XY:

62958

AN XY:

121316

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 SAS exome

AF:

0.417

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

Gnomad4 AFR exome

AF:

0.639

Gnomad4 AMR exome

AF:

0.367

Gnomad4 ASJ exome

AF:

0.510

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.638

Gnomad4 NFE exome

AF:

0.603

Gnomad4 OTH exome

AF:

0.566

GnomAD4 genome

AF:

0.580

AC:

88229

AN:

152062

Hom.:

26266

Cov.:

AF XY:

0.575

AC XY:

42734

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.639

Gnomad4 AMR

AF:

0.490

Gnomad4 ASJ

AF:

0.501

Gnomad4 EAS

AF:

0.235

Gnomad4 SAS

AF:

0.395

Gnomad4 FIN

AF:

0.629

Gnomad4 NFE

AF:

0.599

Gnomad4 OTH

AF:

0.579

Alfa

AF:

0.589

Hom.:

28078

Bravo

AF:

0.572

Asia WGS

AF:

0.364

AC:

1264

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.30

DANN

Benign

0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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