9-72909868-G-T

Variant names:

• chr9-72909868-G-T
• rs63319
• NM_000689.5:c.1201-109C>A

Variant summary

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

The NM_000689.5(ALDH1A1):​c.1201-109C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 952,984 control chromosomes in the GnomAD database, including 125,865 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 0.55 (23791 hom., cov: 32)
  • Exomes 𝑓: 0.50 (102074 hom.)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.1201-109C>A		intron_variant	Intron 10 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.1201-109C>A		intron_variant	Intron 10 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83854 AN: 151798 Hom.: 23760 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.500 AC: 400921 AN: 801068 Hom.: 102074 AF XY: 0.497 AC XY: 200956 AN XY: 404026

Gnomad4 AFR exome AF: 0.707

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.548

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.505

GnomAD4 genome AF: 0.552 AC: 83932 AN: 151916 Hom.: 23791 Cov.: 32 AF XY: 0.550 AC XY: 40790 AN XY: 74230

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.539

Alfa AF: 0.517 Hom.: 9872

Bravo AF: 0.561

Asia WGS AF: 0.534 AC: 1856 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.74

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: rs63319; hg19: chr9-75524784;