9-72904335-C-G

Variant names:

• chr9-72904335-C-G
• rs1888202
• NM_000689.5:c.1433+1623G>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.1433+1623G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,938 control chromosomes in the GnomAD database, including 14,295 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 0.41 (14295 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345
• Publications: 15 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.1433+1623G>C		intron_variant	Intron 12 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.1433+1623G>C		intron_variant	Intron 12 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62054 AN: 151820 Hom.: 14286 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.409 AC: 62079 AN: 151938 Hom.: 14295 Cov.: 32 AF XY: 0.413 AC XY: 30642 AN XY: 74250

African (AFR) AF: 0.176 AC: 7314 AN: 41468

American (AMR) AF: 0.468 AC: 7141 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1814 AN: 3466

East Asian (EAS) AF: 0.443 AC: 2292 AN: 5168

South Asian (SAS) AF: 0.573 AC: 2761 AN: 4816

European-Finnish (FIN) AF: 0.515 AC: 5432 AN: 10552

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33868 AN: 67896

Other (OTH) AF: 0.415 AC: 874 AN: 2106

Alfa AF: 0.428 Hom.: 1865

Bravo AF: 0.391

Asia WGS AF: 0.450 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.61
PhyloP100		0.34
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: rs1888202; hg19: chr9-75519251;