Variant 10-5205821-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001818.5(AKR1C4):c.434C>G(p.Ser145Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,612,174 control chromosomes in the GnomAD database, including 17,158 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1186 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15972 hom. )

Consequence

AKR1C4
NM_001818.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.112

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017965734).

BP6

Variant 10-5205821-C-G is Benign according to our data. Variant chr10-5205821-C-G is described in ClinVar as [Benign]. Clinvar id is 2017865.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKR1C4	NM_001818.5 linkuse as main transcript	c.434C>G	p.Ser145Cys	missense_variant	4/9	ENST00000263126.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1C4	ENST00000263126.3 linkuse as main transcript	c.434C>G	p.Ser145Cys	missense_variant	4/9	1	NM_001818.5	P1
AKR1C4	ENST00000380448.5 linkuse as main transcript	c.434C>G	p.Ser145Cys	missense_variant	6/11	5		P1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17182

AN:

152118

Hom.:

1183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0383

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.138

AC:

34471

AN:

250398

Hom.:

2791

AF XY:

0.136

AC XY:

18413

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.0362

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.104

Gnomad SAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.151

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.144

AC:

210218

AN:

1459938

Hom.:

15972

Cov.:

AF XY:

0.142

AC XY:

103224

AN XY:

726324

show subpopulations

Gnomad4 AFR exome

AF:

0.0326

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.0981

Gnomad4 EAS exome

AF:

0.0898

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.113

AC:

17198

AN:

152236

Hom.:

1186

Cov.:

AF XY:

0.113

AC XY:

8410

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0382

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.110

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.135

Hom.:

514

Bravo

AF:

0.114

TwinsUK

AF:

0.170

AC:

632

ALSPAC

AF:

0.165

AC:

634

ESP6500AA

AF:

0.0420

AC:

185

ESP6500EA

AF:

0.151

AC:

1302

ExAC

AF:

0.137

AC:

16590

Asia WGS

AF:

0.0940

AC:

325

AN:

3478

EpiCase

AF:

0.140

EpiControl

AF:

0.142

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.1

DANN

Benign

0.56

DEOGEN2

Benign

0.030

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0026

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.050

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

7.3

N;N

REVEL

Benign

0.055

Sift

Benign

1.0

T;T

Sift4G

Benign

0.78

T;T

Polyphen

0.0

B;B

Vest4

0.037

MPC

0.015

ClinPred

0.00030

GERP RS

3.2

Varity_R

0.13

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over