Variant 9-38396068-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000692.5(ALDH1B1):c.320G>T(p.Arg107Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,613,740 control chromosomes in the GnomAD database, including 262,050 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 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 0.49 ( 19572 hom., cov: 33)

Exomes 𝑓: 0.57 ( 242478 hom. )

Consequence

ALDH1B1
NM_000692.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.07

Variant links:

Genes affected

ALDH1B1 (HGNC:407): (aldehyde dehydrogenase 1 family member B1) This protein belongs to the aldehyde dehydrogenases family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. This gene does not contain introns in the coding sequence. The variation of this locus may affect the development of alcohol-related problems. [provided by RefSeq, Jul 2008]

ALDH1B1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.0797422E-5).

BP6

Variant 9-38396068-G-T is Benign according to our data. Variant chr9-38396068-G-T is described in ClinVar as [Benign]. Clinvar id is 136362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-38396068-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1B1	NM_000692.5 linkuse as main transcript	c.320G>T	p.Arg107Leu	missense_variant	2/2	ENST00000377698.4	NP_000683.3
ALDH1B1	XM_011517802.3 linkuse as main transcript	c.461G>T	p.Arg154Leu	missense_variant	2/2		XP_011516104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1B1	ENST00000377698.4 linkuse as main transcript	c.320G>T	p.Arg107Leu	missense_variant	2/2	1	NM_000692.5	ENSP00000366927	P1
ALDH1B1	ENST00000635162.1 linkuse as main transcript	c.320G>T	p.Arg107Leu	missense_variant	3/3	3		ENSP00000489053

Frequencies

GnomAD3 genomes

AF:

0.488

AC:

74167

AN:

151934

Hom.:

19573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.824

Gnomad AMR

AF:

0.416

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.518

Gnomad FIN

AF:

0.501

Gnomad MID

AF:

0.662

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.526

GnomAD3 exomes

AF:

0.510

AC:

128169

AN:

251134

Hom.:

34962

AF XY:

0.529

AC XY:

71746

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.311

Gnomad ASJ exome

AF:

0.700

Gnomad EAS exome

AF:

0.316

Gnomad SAS exome

AF:

0.548

Gnomad FIN exome

AF:

0.503

Gnomad NFE exome

AF:

0.604

Gnomad OTH exome

AF:

0.556

GnomAD4 exome

AF:

0.570

AC:

832672

AN:

1461688

Hom.:

242478

Cov.:

AF XY:

0.572

AC XY:

416098

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.303

Gnomad4 AMR exome

AF:

0.326

Gnomad4 ASJ exome

AF:

0.697

Gnomad4 EAS exome

AF:

0.325

Gnomad4 SAS exome

AF:

0.546

Gnomad4 FIN exome

AF:

0.507

Gnomad4 NFE exome

AF:

0.598

Gnomad4 OTH exome

AF:

0.562

GnomAD4 genome

AF:

0.488

AC:

74190

AN:

152052

Hom.:

19572

Cov.:

AF XY:

0.484

AC XY:

35965

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.310

Gnomad4 AMR

AF:

0.416

Gnomad4 ASJ

AF:

0.712

Gnomad4 EAS

AF:

0.309

Gnomad4 SAS

AF:

0.518

Gnomad4 FIN

AF:

0.501

Gnomad4 NFE

AF:

0.605

Gnomad4 OTH

AF:

0.524

Alfa

AF:

0.581

Hom.:

63026

Bravo

AF:

0.472

TwinsUK

AF:

0.602

AC:

2233

ALSPAC

AF:

0.597

AC:

2301

ESP6500AA

AF:

0.307

AC:

1354

ESP6500EA

AF:

0.604

AC:

5192

ExAC

AF:

0.517

AC:

62802

Asia WGS

AF:

0.423

AC:

1477

AN:

3478

EpiCase

AF:

0.620

EpiControl

AF:

0.617

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 05, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

0.040

Eigen_PC

Benign

0.048

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.51

T;T

MetaRNN

Benign

0.000041

T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

0.0026

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-4.8

D;.

REVEL

Uncertain

0.50

Sift

Uncertain

0.0090

D;.

Sift4G

Uncertain

0.0060

D;D

Vest4

0.20

MPC

0.16

ClinPred

0.030

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.54

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