9-72944653-T-G

Variant names:

• chr9-72944653-T-G
• rs3909559
• NM_000689.5:c.67-4401A>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.67-4401A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,870 control chromosomes in the GnomAD database, including 21,744 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 0.52 (21744 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.67-4401A>C		intron_variant	Intron 1 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.67-4401A>C		intron_variant	Intron 1 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79592 AN: 151752 Hom.: 21732 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.524 AC: 79651 AN: 151870 Hom.: 21744 Cov.: 32 AF XY: 0.531 AC XY: 39381 AN XY: 74194

African (AFR) AF: 0.357 AC: 14793 AN: 41448

American (AMR) AF: 0.557 AC: 8467 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2033 AN: 3470

East Asian (EAS) AF: 0.449 AC: 2320 AN: 5162

South Asian (SAS) AF: 0.600 AC: 2888 AN: 4812

European-Finnish (FIN) AF: 0.672 AC: 7091 AN: 10550

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40146 AN: 67920

Other (OTH) AF: 0.540 AC: 1138 AN: 2106

Alfa AF: 0.500 Hom.: 3292

Bravo AF: 0.505

Asia WGS AF: 0.487 AC: 1689 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.53
PhyloP100		0.31
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: rs3909559; hg19: chr9-75559569;