rs348475

Variant names:

• chr9-72910963-G-A
• rs348475
• NM_000689.5:c.1200+995C>T

Variant summary

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

The NM_000689.5(ALDH1A1):​c.1200+995C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,902 control chromosomes in the GnomAD database, including 23,419 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 0.55 (23419 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.1200+995C>T		intron_variant	Intron 10 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.1200+995C>T		intron_variant	Intron 10 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83288 AN: 151784 Hom.: 23396 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.549 AC: 83351 AN: 151902 Hom.: 23419 Cov.: 32 AF XY: 0.546 AC XY: 40510 AN XY: 74226

African (AFR) AF: 0.680 AC: 28208 AN: 41460

American (AMR) AF: 0.500 AC: 7619 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3466

East Asian (EAS) AF: 0.526 AC: 2718 AN: 5170

South Asian (SAS) AF: 0.408 AC: 1961 AN: 4808

European-Finnish (FIN) AF: 0.506 AC: 5327 AN: 10524

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.506 AC: 34336 AN: 67918

Other (OTH) AF: 0.540 AC: 1136 AN: 2104

Alfa AF: 0.517 Hom.: 25898

Bravo AF: 0.557

Asia WGS AF: 0.530 AC: 1834 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.27
DANN	Benign	0.29
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs348475; hg19: chr9-75525879;