rs17134592

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001818.5(AKR1C4):c.931C>G(p.Leu311Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,593,568 control chromosomes in the GnomAD database, including 16,529 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1185 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15344 hom. )

Consequence

AKR1C4
NM_001818.5 missense, splice_region

Scores

Splicing: ADA: 0.00002144

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.50

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=0.010312349).

BP6

Variant 10-5218719-C-G is Benign according to our data. Variant chr10-5218719-C-G is described in ClinVar as [Benign]. Clinvar id is 2017866.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 rank	MANE	Protein	UniProt
AKR1C4	NM_001818.5 link	c.931C>G	p.Leu311Val	missense_variant, splice_region_variant	Exon 9 of 9	ENST00000263126.3	NP_001809.4	P17516

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKR1C4	ENST00000263126.3 link	c.931C>G	p.Leu311Val	missense_variant, splice_region_variant	Exon 9 of 9	1	NM_001818.5	ENSP00000263126.1		P17516
AKR1C4	ENST00000380448.5 link	c.931C>G	p.Leu311Val	missense_variant, splice_region_variant	Exon 11 of 11	5		ENSP00000369814.1		P17516

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17147

AN:

152034

Hom.:

1182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0382

Gnomad AMI

AF:

0.0936

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.136

AC:

34141

AN:

250340

Hom.:

2704

AF XY:

0.135

AC XY:

18232

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.0360

Gnomad AMR exome

AF:

0.201

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.104

Gnomad SAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.141

AC:

203908

AN:

1441416

Hom.:

15344

Cov.:

AF XY:

0.140

AC XY:

100360

AN XY:

718294

show subpopulations

Gnomad4 AFR exome

AF:

0.0321

Gnomad4 AMR exome

AF:

0.202

Gnomad4 ASJ exome

AF:

0.0981

Gnomad4 EAS exome

AF:

0.0897

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.113

AC:

17163

AN:

152152

Hom.:

1185

Cov.:

AF XY:

0.113

AC XY:

8388

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0381

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.115

Hom.:

425

Bravo

AF:

0.114

TwinsUK

AF:

0.170

AC:

629

ALSPAC

AF:

0.164

AC:

631

ESP6500AA

AF:

0.0420

AC:

185

ESP6500EA

AF:

0.151

AC:

1301

ExAC

AF:

0.136

AC:

16478

Asia WGS

AF:

0.0910

AC:

317

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.020

DANN

Benign

0.21

DEOGEN2

Benign

0.040

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00098

LIST_S2

Benign

0.29

.;T

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.010

Sift

Benign

0.45

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.0

B;B

Vest4

0.041

MPC

0.015

ClinPred

0.0016

GERP RS

-5.7

Varity_R

0.12

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over