rs348457

Positions:

• chr9-72915638-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ALDH1A1	NM_000689.5	c.1035+1282G>C		intron_variant		ENST00000297785.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.1035+1282G>C		intron_variant		1	NM_000689.5	P1

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

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.446

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs348457; hg19: chr9-75530554;