dbSNP rs7083869: AKR1C4:c.252+1984G>A (chr10-5202332-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_001818.5(AKR1C4):c.252+1984G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 308,008 control chromosomes in the GnomAD database, including 6,699 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 0.20 ( 3076 hom., cov: 33)

Exomes 𝑓: 0.21 ( 3623 hom. )

Consequence

AKR1C4
NM_001818.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.320

Publications

8 publications found

Variant links:

Genes affected

AKR1C4 (HGNC:387): (aldo-keto reductase family 1 member C4) 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 bioreduction of chlordecone, a toxic organochlorine pesticide, to chlordecone alcohol in liver. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq, Jul 2008]

AKR1C4 Gene-Disease associations (from GenCC):

46,XY disorder of sex development due to testicular 17,20-desmolase deficiency
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

AKR1C4 links:

Genome browser will be placed here

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=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C4	NM_001818.5 link	c.252+1984G>A		intron_variant	Intron 2 of 8	ENST00000263126.3	NP_001809.4	P17516

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C4	ENST00000263126.3 link	c.252+1984G>A		intron_variant	Intron 2 of 8	1	NM_001818.5	ENSP00000263126.1		P17516
AKR1C4	ENST00000380448.5 link	c.252+1984G>A		intron_variant	Intron 4 of 10	5		ENSP00000369814.1		P17516

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30325

AN:

151930

Hom.:

3074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.222

GnomAD4 exome

AF:

0.208

AC:

32461

AN:

155960

Hom.:

3623

AF XY:

0.207

AC XY:

18456

AN XY:

89304

show subpopulations

African (AFR)

AF:

0.236

AC:

1136

AN:

4810

American (AMR)

AF:

0.172

AC:

1880

AN:

10950

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

975

AN:

4556

East Asian (EAS)

AF:

0.262

AC:

1797

AN:

6864

South Asian (SAS)

AF:

0.198

AC:

5635

AN:

28494

European-Finnish (FIN)

AF:

0.220

AC:

1433

AN:

6520

Middle Eastern (MID)

AF:

0.307

AC:

530

AN:

1726

European-Non Finnish (NFE)

AF:

0.205

AC:

17363

AN:

84522

Other (OTH)

AF:

0.228

AC:

1712

AN:

7518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

1165

2331

3496

4662

5827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

296

444

592

740

<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:

0.200

AC:

30343

AN:

152048

Hom.:

3076

Cov.:

AF XY:

0.199

AC XY:

14772

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.222

AC:

9187

AN:

41452

American (AMR)

AF:

0.182

AC:

2785

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

667

AN:

3470

East Asian (EAS)

AF:

0.247

AC:

1277

AN:

5172

South Asian (SAS)

AF:

0.177

AC:

852

AN:

4826

European-Finnish (FIN)

AF:

0.200

AC:

2118

AN:

10568

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12634

AN:

67966

Other (OTH)

AF:

0.224

AC:

473

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1256

2512

3768

5024

6280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.191

Hom.:

5018

Bravo

AF:

0.201

Asia WGS

AF:

0.230

AC:

796

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.32

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over