Genetic Variant NM_000694.4:c.163-442A>C (chr11-68018085-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000694.4(ALDH3B1):c.163-442A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 156,284 control chromosomes in the GnomAD database, including 18,475 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 18036 hom., cov: 33)

Exomes 𝑓: 0.43 ( 439 hom. )

Consequence

ALDH3B1
NM_000694.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.473

Publications

4 publications found

Variant links:

Genes affected

ALDH3B1 (HGNC:410): (aldehyde dehydrogenase 3 family member B1) This gene encodes a member of the aldehyde dehydrogenase protein family. Aldehyde dehydrogenases are a family of isozymes that may play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. The encoded protein is able to oxidize long-chain fatty aldehydes in vitro, and may play a role in protection from oxidative stress. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ALDH3B1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000694.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ALDH3B1	NM_000694.4	MANE Select	c.163-442A>C	intron	N/A	NP_000685.1
ALDH3B1	NM_001161473.3		c.163-442A>C	intron	N/A	NP_001154945.1
ALDH3B1	NM_001030010.3		c.163-688A>C	intron	N/A	NP_001025181.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ALDH3B1	ENST00000342456.11	TSL:1 MANE Select	c.163-442A>C	intron	N/A	ENSP00000473990.2
ALDH3B1	ENST00000614849.4	TSL:1	c.163-442A>C	intron	N/A	ENSP00000478486.1
ALDH3B1	ENST00000617288.4	TSL:1	c.163-688A>C	intron	N/A	ENSP00000481604.1

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

73006

AN:

151928

Hom.:

18017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.583

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.422

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.447

GnomAD4 exome

AF:

0.426

AC:

1805

AN:

4238

Hom.:

439

Cov.:

AF XY:

0.425

AC XY:

989

AN XY:

2326

show subpopulations

African (AFR)

AF:

0.583

AC:

AN:

American (AMR)

AF:

0.246

AC:

AN:

248

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AF:

0.303

AC:

AN:

South Asian (SAS)

AF:

0.374

AC:

175

AN:

468

European-Finnish (FIN)

AF:

0.439

AC:

AN:

148

Middle Eastern (MID)

AF:

0.143

AC:

AN:

European-Non Finnish (NFE)

AF:

0.453

AC:

1320

AN:

2914

Other (OTH)

AF:

0.430

AC:

104

AN:

242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

148

198

247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.481

AC:

73072

AN:

152046

Hom.:

18036

Cov.:

AF XY:

0.474

AC XY:

35252

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.583

AC:

24184

AN:

41482

American (AMR)

AF:

0.387

AC:

5925

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1361

AN:

3470

East Asian (EAS)

AF:

0.372

AC:

1908

AN:

5132

South Asian (SAS)

AF:

0.395

AC:

1904

AN:

4824

European-Finnish (FIN)

AF:

0.422

AC:

4462

AN:

10568

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.466

AC:

31698

AN:

67960

Other (OTH)

AF:

0.445

AC:

938

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1972

3944

5916

7888

9860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<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:

0.462

Hom.:

2705

Bravo

AF:

0.481

Asia WGS

AF:

0.390

AC:

1356

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

(source)

DANN

Benign

0.66

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over