9-72992968-T-C

Position:

• chr9-72992968-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000419959.5(ALDH1A1):​c.-14-39954A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,940 control chromosomes in the GnomAD database, including 18,143 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 (18143 hom., cov: 32)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000419959.5	c.-14-39954A>G		intron_variant		5		ENSP00000388026
ALDH1A1	ENST00000446946.1	c.-14-39954A>G		intron_variant		5		ENSP00000401361

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69847 AN: 151824 Hom.: 18139 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.460 AC: 69865 AN: 151940 Hom.: 18143 Cov.: 32 AF XY: 0.466 AC XY: 34594 AN XY: 74220

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.492

Alfa AF: 0.514 Hom.: 4218

Bravo AF: 0.437

Asia WGS AF: 0.436 AC: 1518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.88
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11143429; hg19: chr9-75607884;