Variant chr7-138088656-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005989.4(AKR1D1):c.149G>A(p.Arg50Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

AKR1D1
NM_005989.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Variant links:

Genes affected

AKR1D1 (HGNC:388): (aldo-keto reductase family 1 member D1) The enzyme encoded by this gene is responsible for the catalysis of the 5-beta-reduction of bile acid intermediates and steroid hormones carrying a delta(4)-3-one structure. Deficiency of this enzyme may contribute to hepatic dysfunction. Three transcript variants encoding different isoforms have been found for this gene. Other variants may be present, but their full-length natures have not been determined yet. [provided by RefSeq, Jul 2010]

AKR1D1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16116086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AKR1D1	NM_005989.4 linkuse as main transcript	c.149G>A	p.Arg50Gln	missense_variant	2/9	ENST00000242375.8
AKR1D1	NM_001190907.2 linkuse as main transcript	c.149G>A	p.Arg50Gln	missense_variant	2/8
AKR1D1	NM_001190906.2 linkuse as main transcript	c.149G>A	p.Arg50Gln	missense_variant	2/8
AKR1D1	XM_047420763.1 linkuse as main transcript	c.94-3112G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKR1D1	ENST00000242375.8 linkuse as main transcript	c.149G>A	p.Arg50Gln	missense_variant	2/9	1	NM_005989.4	P1	P51857-1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000223

AC:

AN:

251136

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000118

AC:

173

AN:

1461798

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00146

Gnomad4 NFE exome

AF:

0.0000683

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000217

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000118

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000280

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.061

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Pathogenic

3.5

H;H;H

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.40

MVP

0.70

MPC

0.37

ClinPred

0.82

GERP RS

5.4

Varity_R

0.85

gMVP

0.93

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