9-38396005-C-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.257C>T(p.Ala86Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,532 control chromosomes in the GnomAD database, including 21,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2055 hom., cov: 34)

Exomes 𝑓: 0.15 ( 19511 hom. )

Consequence

ALDH1B1
NM_000692.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.55

Publications

40 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=0.0030218363).

BP6

Variant 9-38396005-C-T is Benign according to our data. Variant chr9-38396005-C-T is described in ClinVar as Benign. ClinVar VariationId is 136361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1B1	NM_000692.5 link	c.257C>T	p.Ala86Val	missense_variant	Exon 2 of 2	ENST00000377698.4	NP_000683.3
ALDH1B1	XM_011517802.3 link	c.398C>T	p.Ala133Val	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.257C>T	p.Ala86Val	missense_variant	Exon 2 of 2	1	NM_000692.5	ENSP00000366927.3
ALDH1B1	ENST00000635162.1 link	c.257C>T	p.Ala86Val	missense_variant	Exon 3 of 3	3		ENSP00000489053.1

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22596

AN:

152090

Hom.:

2047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0954

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.147

GnomAD2 exomes

AF:

0.194

AC:

48473

AN:

250432

AF XY:

0.191

show subpopulations

Gnomad AFR exome

AF:

0.0941

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.378

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.163

GnomAD4 exome

AF:

0.153

AC:

222885

AN:

1461324

Hom.:

19511

Cov.:

101

AF XY:

0.155

AC XY:

112717

AN XY:

727000

show subpopulations

African (AFR)

AF:

0.0929

AC:

3111

AN:

33480

American (AMR)

AF:

0.315

AC:

14075

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3710

AN:

26132

East Asian (EAS)

AF:

0.362

AC:

14361

AN:

39698

South Asian (SAS)

AF:

0.254

AC:

21950

AN:

86250

European-Finnish (FIN)

AF:

0.182

AC:

9644

AN:

52902

Middle Eastern (MID)

AF:

0.169

AC:

977

AN:

5768

European-Non Finnish (NFE)

AF:

0.131

AC:

145535

AN:

1111978

Other (OTH)

AF:

0.158

AC:

9522

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

13146

26292

39438

52584

65730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5572

11144

16716

22288

27860

<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:

0.149

AC:

22622

AN:

152208

Hom.:

2055

Cov.:

AF XY:

0.155

AC XY:

11542

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0954

AC:

3963

AN:

41558

American (AMR)

AF:

0.232

AC:

3542

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

485

AN:

3468

East Asian (EAS)

AF:

0.384

AC:

1980

AN:

5154

South Asian (SAS)

AF:

0.271

AC:

1309

AN:

4822

European-Finnish (FIN)

AF:

0.177

AC:

1875

AN:

10592

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.133

AC:

9023

AN:

68004

Other (OTH)

AF:

0.152

AC:

322

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

962

1924

2885

3847

4809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.140

Hom.:

5275

Bravo

AF:

0.151

TwinsUK

AF:

0.127

AC:

472

ALSPAC

AF:

0.134

AC:

517

ESP6500AA

AF:

0.107

AC:

472

ESP6500EA

AF:

0.133

AC:

1143

ExAC

AF:

0.185

AC:

22419

Asia WGS

AF:

0.303

AC:

1051

AN:

3478

EpiCase

AF:

0.128

EpiControl

AF:

0.128

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 29, 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

.;T

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-1.0

PhyloP100

7.5

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.6

D;.

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Vest4

0.75

MPC

0.49

ClinPred

0.017

GERP RS

5.5

gMVP

0.76

Mutation Taster

=82/18

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