9-72979640-G-T

Variant names:

• chr9-72979640-G-T
• rs7858367
• ENST00000419959.5:c.-14-26626C>A

Variant summary

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

The ENST00000419959.5(ALDH1A1):​c.-14-26626C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,836 control chromosomes in the GnomAD database, including 17,973 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 0.46 (17973 hom., cov: 31)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507
• Publications: 3 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000419959.5	c.-14-26626C>A		intron_variant	Intron 1 of 7	5		ENSP00000388026.1
ALDH1A1	ENST00000446946.1	c.-14-26626C>A		intron_variant	Intron 1 of 6	5		ENSP00000401361.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69083 AN: 151718 Hom.: 17971 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.455 AC: 69093 AN: 151836 Hom.: 17973 Cov.: 31 AF XY: 0.461 AC XY: 34228 AN XY: 74186

African (AFR) AF: 0.187 AC: 7772 AN: 41462

American (AMR) AF: 0.516 AC: 7845 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3466

East Asian (EAS) AF: 0.424 AC: 2176 AN: 5136

South Asian (SAS) AF: 0.512 AC: 2463 AN: 4812

European-Finnish (FIN) AF: 0.643 AC: 6780 AN: 10552

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38619 AN: 67888

Other (OTH) AF: 0.488 AC: 1026 AN: 2102

Alfa AF: 0.526 Hom.: 34813

Bravo AF: 0.431

Asia WGS AF: 0.429 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.48
PhyloP100		0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7858367; hg19: chr9-75594556;