Variant 9-38396005-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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, single submitter B:1

Conservation

PhyloP100: 7.55

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 id is 136361.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
ALDH1B1	NM_000692.5 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	2/2	ENST00000377698.4
ALDH1B1	XM_011517802.3 linkuse as main transcript	c.398C>T	p.Ala133Val	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1B1	ENST00000377698.4 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	2/2	1	NM_000692.5	P1
ALDH1B1	ENST00000635162.1 linkuse as main transcript	c.257C>T	p.Ala86Val	missense_variant	3/3	3

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

GnomAD3 exomes

AF:

0.194

AC:

48473

AN:

250432

Hom.:

5814

AF XY:

0.191

AC XY:

25832

AN XY:

135472

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 SAS exome

AF:

0.252

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

Gnomad4 AFR exome

AF:

0.0929

Gnomad4 AMR exome

AF:

0.315

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.362

Gnomad4 SAS exome

AF:

0.254

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.149

AC:

22622

AN:

152208

Hom.:

2055

Cov.:

AF XY:

0.155

AC XY:

11542

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0954

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.384

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.177

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.152

Alfa

AF:

0.138

Hom.:

3454

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 29, 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. -

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

DANN

Pathogenic

1.0

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

MutationTaster

Benign

3.4e-7

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

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