rs348457

Variant names:

• chr9-72915638-C-G
• rs348457
• NM_000689.5:c.1035+1282G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000689.5(ALDH1A1):​c.1035+1282G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,958 control chromosomes in the GnomAD database, including 14,273 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 0.43 (14273 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 10 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.1035+1282G>C		intron_variant	Intron 9 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.1035+1282G>C		intron_variant	Intron 9 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65710 AN: 151840 Hom.: 14276 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.443

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.433 AC: 65723 AN: 151958 Hom.: 14273 Cov.: 32 AF XY: 0.429 AC XY: 31851 AN XY: 74266

African (AFR) AF: 0.423 AC: 17537 AN: 41470

American (AMR) AF: 0.444 AC: 6782 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1275 AN: 3468

East Asian (EAS) AF: 0.520 AC: 2673 AN: 5144

South Asian (SAS) AF: 0.350 AC: 1686 AN: 4814

European-Finnish (FIN) AF: 0.413 AC: 4367 AN: 10562

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.441 AC: 29945 AN: 67920

Other (OTH) AF: 0.446 AC: 941 AN: 2108

Alfa AF: 0.441 Hom.: 1849

Bravo AF: 0.439

Asia WGS AF: 0.468 AC: 1627 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.50
PhyloP100		-0.054
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs348457; hg19: chr9-75530554;