dbSNP rs11597709: AKR1C3:c.85-16176G>A (chr10-5080234-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_001253908.2(AKR1C3):c.85-16176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 152,238 control chromosomes in the GnomAD database, including 194 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 0.049 ( 194 hom., cov: 33)

Consequence

AKR1C3
NM_001253908.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0220

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:

LOC107984198 (HGNC:):

LOC107984198 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253908.2. 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_001253908.2		c.85-16176G>A		intron	N/A	NP_001240837.1	A0A0A0MSS8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AKR1C3	ENST00000439082.7	TSL:5	c.85-16176G>A	intron	N/A	ENSP00000401327.3	A0A0A0MSS8
AKR1C3	ENST00000605149.5	TSL:2	c.15+2257G>A	intron	N/A	ENSP00000474882.1	S4R3Z2
AKR1C3	ENST00000602997.5	TSL:3	c.15+2257G>A	intron	N/A	ENSP00000474188.1	S4R3D5

Frequencies

GnomAD3 genomes

AF:

0.0493

AC:

7502

AN:

152120

Hom.:

195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0247

Gnomad AMI

AF:

0.0725

Gnomad AMR

AF:

0.0479

Gnomad ASJ

AF:

0.0717

Gnomad EAS

AF:

0.0235

Gnomad SAS

AF:

0.0400

Gnomad FIN

AF:

0.0304

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0678

Gnomad OTH

AF:

0.0713

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

GnomAD4 genome

AF:

0.0492

AC:

7497

AN:

152238

Hom.:

194

Cov.:

AF XY:

0.0471

AC XY:

3507

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0246

AC:

1022

AN:

41544

American (AMR)

AF:

0.0479

AC:

732

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0717

AC:

249

AN:

3472

East Asian (EAS)

AF:

0.0232

AC:

120

AN:

5172

South Asian (SAS)

AF:

0.0396

AC:

191

AN:

4820

European-Finnish (FIN)

AF:

0.0304

AC:

323

AN:

10612

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0678

AC:

4609

AN:

68006

Other (OTH)

AF:

0.0710

AC:

150

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

362

724

1085

1447

1809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0597

Hom.:

517

Bravo

AF:

0.0492

Asia WGS

AF:

0.0480

AC:

168

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.7

(source)

DANN

Benign

0.60

PhyloP100

0.022

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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