Variant chr9-38395943-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000377698.4(ALDH1B1):c.195T>C(p.Ile65=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 1,613,730 control chromosomes in the GnomAD database, including 737,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 66002 hom., cov: 33)

Exomes 𝑓: 0.96 ( 671046 hom. )

Consequence

ALDH1B1
ENST00000377698.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.640

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-38395943-T-C is Benign according to our data. Variant chr9-38395943-T-C is described in ClinVar as [Benign]. Clinvar id is 136360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-38395943-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.195T>C	p.Ile65=	synonymous_variant	2/2	ENST00000377698.4	NP_000683.3
ALDH1B1	XM_011517802.3 linkuse as main transcript	c.336T>C	p.Ile112=	synonymous_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.195T>C	p.Ile65=	synonymous_variant	2/2	1	NM_000692.5	ENSP00000366927	P1
ALDH1B1	ENST00000635162.1 linkuse as main transcript	c.195T>C	p.Ile65=	synonymous_variant	3/3	3		ENSP00000489053

Frequencies

GnomAD3 genomes

AF:

0.930

AC:

141476

AN:

152132

Hom.:

65961

Cov.:

show subpopulations

Gnomad AFR

AF:

0.849

Gnomad AMI

AF:

0.984

Gnomad AMR

AF:

0.957

Gnomad ASJ

AF:

0.960

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.984

Gnomad FIN

AF:

0.945

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.959

Gnomad OTH

AF:

0.932

GnomAD3 exomes

AF:

0.957

AC:

240166

AN:

250944

Hom.:

115046

AF XY:

0.959

AC XY:

130150

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.847

Gnomad AMR exome

AF:

0.974

Gnomad ASJ exome

AF:

0.956

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.981

Gnomad FIN exome

AF:

0.948

Gnomad NFE exome

AF:

0.956

Gnomad OTH exome

AF:

0.955

GnomAD4 exome

AF:

0.958

AC:

1400238

AN:

1461480

Hom.:

671046

Cov.:

AF XY:

0.959

AC XY:

697480

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.847

Gnomad4 AMR exome

AF:

0.971

Gnomad4 ASJ exome

AF:

0.956

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.981

Gnomad4 FIN exome

AF:

0.944

Gnomad4 NFE exome

AF:

0.959

Gnomad4 OTH exome

AF:

0.955

GnomAD4 genome

AF:

0.930

AC:

141577

AN:

152250

Hom.:

66002

Cov.:

AF XY:

0.931

AC XY:

69299

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.849

Gnomad4 AMR

AF:

0.957

Gnomad4 ASJ

AF:

0.960

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.984

Gnomad4 FIN

AF:

0.945

Gnomad4 NFE

AF:

0.959

Gnomad4 OTH

AF:

0.932

Alfa

AF:

0.953

Hom.:

90155

Bravo

AF:

0.927

Asia WGS

AF:

0.980

AC:

3408

AN:

3478

EpiCase

AF:

0.955

EpiControl

AF:

0.953

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 09, 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

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.14

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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