Genetic Variant ALDH1B1:p.Arg18Leu (chr9-38395801-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000692.5(ALDH1B1):c.53G>T(p.Arg18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R18C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ALDH1B1
NM_000692.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058257133).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000692.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1B1	NM_000692.5	MANE Select	c.53G>T	p.Arg18Leu	missense	Exon 2 of 2	NP_000683.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALDH1B1	ENST00000377698.4	TSL:1 MANE Select	c.53G>T	p.Arg18Leu	missense	Exon 2 of 2	ENSP00000366927.3	P30837
ALDH1B1	ENST00000897464.1		c.53G>T	p.Arg18Leu	missense	Exon 2 of 2	ENSP00000567523.1
ALDH1B1	ENST00000897465.1		c.53G>T	p.Arg18Leu	missense	Exon 2 of 2	ENSP00000567524.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726348

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86172

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111734

Other (OTH)

AF:

0.00

AC:

AN:

60370

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.012

(source)

DANN

Benign

0.32

DEOGEN2

Benign

0.0093

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.18

M_CAP

Benign

0.023

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

PhyloP100

-1.1

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.46

REVEL

Benign

0.14

Sift

Benign

0.40

Sift4G

Benign

0.33

Vest4

0.17

MutPred

0.46

Loss of MoRF binding (P = 0.0079)

MVP

0.43

MPC

0.12

ClinPred

0.020

GERP RS

-3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.53

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over