Variant 10-5200201-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001818.5(AKR1C4):c.105A>G(p.Val35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,736 control chromosomes in the GnomAD database, including 39,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2875 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36440 hom. )

Consequence

AKR1C4
NM_001818.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.62

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 10-5200201-A-G is Benign according to our data. Variant chr10-5200201-A-G is described in ClinVar as [Benign]. Clinvar id is 1229360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKR1C4	NM_001818.5 linkuse as main transcript	c.105A>G	p.Val35=	synonymous_variant	2/9	ENST00000263126.3	NP_001809.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKR1C4	ENST00000263126.3 linkuse as main transcript	c.105A>G	p.Val35=	synonymous_variant	2/9	1	NM_001818.5	ENSP00000263126	P1
AKR1C4	ENST00000380448.5 linkuse as main transcript	c.105A>G	p.Val35=	synonymous_variant	4/11	5		ENSP00000369814	P1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28388

AN:

152188

Hom.:

2874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.205

AC:

51326

AN:

250916

Hom.:

5552

AF XY:

0.205

AC XY:

27749

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.240

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.166

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.232

Gnomad OTH exome

AF:

0.214

GnomAD4 exome

AF:

0.220

AC:

320870

AN:

1461430

Hom.:

36440

Cov.:

AF XY:

0.217

AC XY:

157978

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.164

Gnomad4 FIN exome

AF:

0.199

Gnomad4 NFE exome

AF:

0.233

Gnomad4 OTH exome

AF:

0.209

GnomAD4 genome

AF:

0.186

AC:

28402

AN:

152306

Hom.:

2875

Cov.:

AF XY:

0.185

AC XY:

13791

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.227

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.215

Hom.:

2487

Bravo

AF:

0.187

Asia WGS

AF:

0.144

AC:

503

AN:

3478

EpiCase

AF:

0.221

EpiControl

AF:

0.224

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 15, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.31

DANN

Benign

0.55

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over