rs8187919

Positions:

• chr9-72929881-A-G

Variant summary

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

The NM_000689.5(ALDH1A1):​c.313-860T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 152,298 control chromosomes in the GnomAD database, including 254 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 0.045 (254 hom., cov: 33)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A1	NM_000689.5	c.313-860T>C		intron_variant		ENST00000297785.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.313-860T>C		intron_variant		1	NM_000689.5	P1

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 6822 AN: 152180 Hom.: 253 Cov.: 33

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0425

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

GnomAD4 genome AF: 0.0449 AC: 6833 AN: 152298 Hom.: 254 Cov.: 33 AF XY: 0.0443 AC XY: 3298 AN XY: 74472

Gnomad4 AFR AF: 0.0852

Gnomad4 AMR AF: 0.0254

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0800

Gnomad4 FIN AF: 0.0196

Gnomad4 NFE AF: 0.0247

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0313 Hom.: 114

Bravo AF: 0.0464

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.3
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs8187919; hg19: chr9-75544797;