9-38396068-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R107C) has been classified as Uncertain significance.

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

Publications

49 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ALDH1B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 136362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ALDH1B1	NM_000692.5 link	c.320G>T	p.Arg107Leu	missense_variant	Exon 2 of 2	ENST00000377698.4	NP_000683.3
ALDH1B1	XM_011517802.3 link	c.461G>T	p.Arg154Leu	missense_variant	Exon 2 of 2		XP_011516104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1B1	ENST00000377698.4 link	c.320G>T	p.Arg107Leu	missense_variant	Exon 2 of 2	1	NM_000692.5	ENSP00000366927.3
ALDH1B1	ENST00000635162.1 link	c.320G>T	p.Arg107Leu	missense_variant	Exon 3 of 3	3		ENSP00000489053.1

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

GnomAD2 exomes

AF:

0.510

AC:

128169

AN:

251134

AF XY:

0.529

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 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

African (AFR)

AF:

0.303

AC:

10133

AN:

33476

American (AMR)

AF:

0.326

AC:

14561

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.697

AC:

18216

AN:

26130

East Asian (EAS)

AF:

0.325

AC:

12896

AN:

39694

South Asian (SAS)

AF:

0.546

AC:

47081

AN:

86256

European-Finnish (FIN)

AF:

0.507

AC:

27022

AN:

53332

Middle Eastern (MID)

AF:

0.588

AC:

3391

AN:

5768

European-Non Finnish (NFE)

AF:

0.598

AC:

665423

AN:

1111924

Other (OTH)

AF:

0.562

AC:

33949

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

25084

50168

75251

100335

125419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17850

35700

53550

71400

89250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.488

AC:

74190

AN:

152052

Hom.:

19572

Cov.:

AF XY:

0.484

AC XY:

35965

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.310

AC:

12850

AN:

41490

American (AMR)

AF:

0.416

AC:

6353

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.712

AC:

2469

AN:

3470

East Asian (EAS)

AF:

0.309

AC:

1592

AN:

5148

South Asian (SAS)

AF:

0.518

AC:

2496

AN:

4818

European-Finnish (FIN)

AF:

0.501

AC:

5305

AN:

10580

Middle Eastern (MID)

AF:

0.668

AC:

195

AN:

292

European-Non Finnish (NFE)

AF:

0.605

AC:

41075

AN:

67948

Other (OTH)

AF:

0.524

AC:

1105

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1812

3625

5437

7250

9062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

662

1324

1986

2648

3310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.568

Hom.:

116401

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

Sep 05, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0

.;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

MutationAssessor

Benign

0.0

.;.

PhyloP100

3.1

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

ClinPred

0.030

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.54

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over