rs348449

Positions:

• chr9-72940066-G-A
• chr9-72940066-G-C

Variant summary

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

The NM_000689.5(ALDH1A1):​c.171+82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 987,102 control chromosomes in the GnomAD database, including 454,441 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 0.94 (66769 hom., cov: 26)
  • Exomes 𝑓: 0.96 (387672 hom.)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747

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]

ALDH1A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.171+82C>T		intron_variant		ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.171+82C>T		intron_variant		1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.938 AC: 141849 AN: 151202 Hom.: 66719 Cov.: 26

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.945

GnomAD4 exome AF: 0.963 AC: 804688 AN: 835786 Hom.: 387672 AF XY: 0.961 AC XY: 418244 AN XY: 435082

Gnomad4 AFR exome AF: 0.856

Gnomad4 AMR exome AF: 0.980

Gnomad4 ASJ exome AF: 0.979

Gnomad4 EAS exome AF: 0.959

Gnomad4 SAS exome AF: 0.925

Gnomad4 FIN exome AF: 0.975

Gnomad4 NFE exome AF: 0.969

Gnomad4 OTH exome AF: 0.957

GnomAD4 genome AF: 0.938 AC: 141959 AN: 151316 Hom.: 66769 Cov.: 26 AF XY: 0.939 AC XY: 69344 AN XY: 73854

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.966

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.960

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.980

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.946

Alfa AF: 0.964 Hom.: 66443

Bravo AF: 0.934

Asia WGS AF: 0.930 AC: 3235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.22

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: rs348449; hg19: chr9-75554982;