Variant rs11474 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001393392.1(AKR1C2):c.515T>A(p.Leu172Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00028 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

AKR1C2
NM_001393392.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66

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 links:

AKR1C2 (HGNC:):

AKR1C2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029745638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C2	NM_001393392.1 linkuse as main transcript	c.515T>A	p.Leu172Gln	missense_variant	5/9	ENST00000380753.9	NP_001380321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AKR1C2	ENST00000380753.9 linkuse as main transcript	c.515T>A	p.Leu172Gln	missense_variant	5/9	1	NM_001393392.1	ENSP00000370129.4	P52895-1
AKR1C2	ENST00000421196.7 linkuse as main transcript	c.437T>A	p.Leu146Gln	missense_variant	4/8	1		ENSP00000392694.2	B4DK69
AKR1C2	ENST00000604507.5 linkuse as main transcript	c.515T>A	p.Leu172Gln	missense_variant	6/7	5		ENSP00000474566.1	S4R3P0
AKR1C2	ENST00000460124.5 linkuse as main transcript	n.1975T>A		non_coding_transcript_exon_variant	4/8	5

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

251446

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000283

AC:

413

AN:

1461814

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

208

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000346

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000256

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000150

Hom.:

Bravo

AF:

0.000223

ExAC

AF:

0.000157

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.2

DANN

Benign

0.83

DEOGEN2

Benign

0.029

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.030

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.7

N;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

5.7

N;N;.

REVEL

Benign

0.042

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

B;B;.

Vest4

0.32

MVP

0.11

MPC

0.12

ClinPred

0.0023

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.26

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