rs1418187

chr9-73022744-G-Achr9-73022744-G-C

Variant summary

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

The ENST00000419959.5(ALDH1A1):c.-15+57623C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,822 control chromosomes in the GnomAD database, including 10,980 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 0.36 (10980 hom., cov: 32)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A1	ENST00000419959.5	c.-15+57623C>T		intron_variant		5
ALDH1A1	ENST00000446946.1	c.-15+15797C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54208 AN: 151704 Hom.: 10969 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.357 AC: 54260 AN: 151822 Hom.: 10980 Cov.: 32 AF XY: 0.356 AC XY: 26432 AN XY: 74206

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.332

Alfa AF: 0.322 Hom.: 1040

Bravo AF: 0.377

Asia WGS AF: 0.434 AC: 1505 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.3
Dann	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1418187; hg19: chr9-75637660;