9-72948641-C-T

Variant names:

• chr9-72948641-C-T
• rs1424482
• NM_000689.5:c.66+4294G>A

Variant summary

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

The NM_000689.5(ALDH1A1):​c.66+4294G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,686 control chromosomes in the GnomAD database, including 24,238 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 (24238 hom., cov: 31)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 18 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000689.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	NM_000689.5	MANE Select	c.66+4294G>A		intron	N/A	NP_000680.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	ENST00000297785.8	TSL:1 MANE Select	c.66+4294G>A		intron	N/A	ENSP00000297785.3
	ALDH1A1	ENST00000419959.5	TSL:5	c.66+4294G>A		intron	N/A	ENSP00000388026.1
	ALDH1A1	ENST00000376939.5	TSL:5	c.66+4294G>A		intron	N/A	ENSP00000366138.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82835 AN: 151568 Hom.: 24227 Cov.: 31

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.546 AC: 82886 AN: 151686 Hom.: 24238 Cov.: 31 AF XY: 0.551 AC XY: 40842 AN XY: 74116

African (AFR) AF: 0.335 AC: 13883 AN: 41402

American (AMR) AF: 0.581 AC: 8821 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1836 AN: 3462

East Asian (EAS) AF: 0.419 AC: 2154 AN: 5140

South Asian (SAS) AF: 0.572 AC: 2756 AN: 4820

European-Finnish (FIN) AF: 0.723 AC: 7640 AN: 10568

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.646 AC: 43794 AN: 67816

Other (OTH) AF: 0.569 AC: 1197 AN: 2104

Alfa AF: 0.610 Hom.: 48957

Bravo AF: 0.525

Asia WGS AF: 0.465 AC: 1620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.20
PhyloP100		-0.070
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: rs1424482; hg19: chr9-75563557;