rs6560311

Variant names:

• chr9-72997266-G-T
• rs6560311
• ENST00000419959.5:c.-14-44252C>A

Variant summary

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

The ENST00000419959.5(ALDH1A1):​c.-14-44252C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,098 control chromosomes in the GnomAD database, including 8,413 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 0.33 (8413 hom., cov: 33)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 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.-14-44252C>A		intron_variant	Intron 1 of 7	5		ENSP00000388026.1
ALDH1A1	ENST00000446946.1	c.-15+41275C>A		intron_variant	Intron 1 of 6	5		ENSP00000401361.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49979 AN: 151980 Hom.: 8411 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.329 AC: 50008 AN: 152098 Hom.: 8413 Cov.: 33 AF XY: 0.327 AC XY: 24293 AN XY: 74354

African (AFR) AF: 0.342 AC: 14188 AN: 41506

American (AMR) AF: 0.354 AC: 5400 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1291 AN: 3472

East Asian (EAS) AF: 0.519 AC: 2688 AN: 5176

South Asian (SAS) AF: 0.330 AC: 1594 AN: 4826

European-Finnish (FIN) AF: 0.246 AC: 2594 AN: 10554

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21225 AN: 67976

Other (OTH) AF: 0.323 AC: 683 AN: 2114

Alfa AF: 0.337 Hom.: 3299

Bravo AF: 0.339

Asia WGS AF: 0.422 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.084
DANN	Benign	0.80
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs6560311; hg19: chr9-75612182;