Genetic Variant NM_000689.5:c.*315G>C (chr9-72900893-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000689.5(ALDH1A1):c.*315G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 204,484 control chromosomes in the GnomAD database, including 54 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 0.019 ( 36 hom., cov: 32)

Exomes 𝑓: 0.024 ( 18 hom. )

Consequence

ALDH1A1
NM_000689.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0340

Publications

5 publications found

Variant links:

Genes affected

ALDH1A1 (HGNC:402): (aldehyde dehydrogenase 1 family member A1) The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet. [provided by RefSeq, Mar 2011]

ALDH1A1 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=-0.65).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0191 (2901/152102) while in subpopulation SAS AF = 0.0332 (160/4818). AF 95% confidence interval is 0.029. There are 36 homozygotes in GnomAd4. There are 1457 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2901 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5 link	c.*315G>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8 link	c.*315G>C		3_prime_UTR_variant	Exon 13 of 13	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2903

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00517

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.00938

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.0270

Gnomad SAS

AF:

0.0332

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0272

Gnomad OTH

AF:

0.0168

GnomAD4 exome

AF:

0.0237

AC:

1239

AN:

52382

Hom.:

Cov.:

AF XY:

0.0234

AC XY:

640

AN XY:

27392

show subpopulations

African (AFR)

AF:

0.00626

AC:

AN:

1918

American (AMR)

AF:

0.00874

AC:

AN:

3434

Ashkenazi Jewish (ASJ)

AF:

0.00826

AC:

AN:

1816

East Asian (EAS)

AF:

0.0214

AC:

AN:

4296

South Asian (SAS)

AF:

0.0374

AC:

125

AN:

3340

European-Finnish (FIN)

AF:

0.0389

AC:

AN:

1722

Middle Eastern (MID)

AF:

0.0395

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.0256

AC:

835

AN:

32554

Other (OTH)

AF:

0.0176

AC:

AN:

3074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

125

187

250

312

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:

0.0191

AC:

2901

AN:

152102

Hom.:

Cov.:

AF XY:

0.0196

AC XY:

1457

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00515

AC:

214

AN:

41540

American (AMR)

AF:

0.00936

AC:

143

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3470

East Asian (EAS)

AF:

0.0273

AC:

141

AN:

5172

South Asian (SAS)

AF:

0.0332

AC:

160

AN:

4818

European-Finnish (FIN)

AF:

0.0267

AC:

283

AN:

10582

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0272

AC:

1845

AN:

67938

Other (OTH)

AF:

0.0161

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

147

294

441

588

735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0241

Hom.:

Bravo

AF:

0.0166

Asia WGS

AF:

0.0310

AC:

107

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.1

(source)

DANN

Benign

0.70

PhyloP100

-0.034

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=93/7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over