Genetic Variant NM_001393392.1:c.570+1253C>T (chr10-4997372-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_001393392.1(AKR1C2):c.570+1253C>T 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 152,284 control chromosomes in the GnomAD database, including 4,024 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 ( 4018 hom., cov: 32)

Exomes 𝑓: 0.17 ( 6 hom. )

Consequence

AKR1C2
NM_001393392.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0100

Publications

2 publications found

Variant links:

Genes affected

AKR1C2 (HGNC:385): (aldo-keto reductase family 1 member C2) 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 using NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme binds bile acid with high affinity, and shows minimal 3-alpha-hydroxysteroid dehydrogenase activity. 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 two different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

AKR1C2 Gene-Disease associations (from GenCC):

46,XY disorder of sex development due to testicular 17,20-desmolase deficiency
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

AKR1C2 links:

ENSG00000224251 (HGNC:):

ENSG00000224251 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKR1C2	NM_001393392.1 link	c.570+1253C>T		intron_variant	Intron 5 of 8	ENST00000380753.9	NP_001380321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C2	ENST00000380753.9 link	c.570+1253C>T		intron_variant	Intron 5 of 8	1	NM_001393392.1	ENSP00000370129.4

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31040

AN:

151904

Hom.:

4013

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0868

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.173

AC:

AN:

260

Hom.:

Cov.:

AF XY:

0.158

AC XY:

AN XY:

152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.222

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.131

AC:

AN:

214

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.204

AC:

31063

AN:

152024

Hom.:

4018

Cov.:

AF XY:

0.215

AC XY:

15969

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.111

AC:

4595

AN:

41510

American (AMR)

AF:

0.311

AC:

4753

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

562

AN:

3468

East Asian (EAS)

AF:

0.599

AC:

3085

AN:

5148

South Asian (SAS)

AF:

0.399

AC:

1922

AN:

4814

European-Finnish (FIN)

AF:

0.225

AC:

2372

AN:

10554

Middle Eastern (MID)

AF:

0.269

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.193

AC:

13142

AN:

67948

Other (OTH)

AF:

0.225

AC:

475

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1184

2368

3551

4735

5919

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.197

Hom.:

1296

Bravo

AF:

0.208

Asia WGS

AF:

0.418

AC:

1449

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

(source)

DANN

Benign

0.64

PhyloP100

-0.010

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