rs13959

chr9-72930966-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000689.5(ALDH1A1):c.225C>T(p.Ser75=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,613,406 control chromosomes in the GnomAD database, including 199,816 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 0.43 (15080 hom., cov: 32)
  • Exomes 𝑓: 0.50 (184736 hom.)
• Consequence: ALDH1A1 NM_000689.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-1.53 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A1	NM_000689.5	c.225C>T	p.Ser75=	synonymous_variant	3/13	ENST00000297785.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.225C>T	p.Ser75=	synonymous_variant	3/13	1	NM_000689.5	P1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64933 AN: 151826 Hom.: 15072 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.436

GnomAD3 exomes AF: 0.476 AC: 119437 AN: 250974 Hom.: 29129 AF XY: 0.481 AC XY: 65288 AN XY: 135642

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.466

Gnomad SAS exome AF: 0.490

Gnomad FIN exome AF: 0.534

Gnomad NFE exome AF: 0.498

Gnomad OTH exome AF: 0.489

GnomAD4 exome AF: 0.500 AC: 730120 AN: 1461462 Hom.: 184736 Cov.: 47 AF XY: 0.500 AC XY: 363283 AN XY: 727052

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.484

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.434

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.531

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.477

GnomAD4 genome AF: 0.428 AC: 64984 AN: 151944 Hom.: 15080 Cov.: 32 AF XY: 0.433 AC XY: 32158 AN XY: 74272

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.434

Alfa AF: 0.481 Hom.: 34840

Bravo AF: 0.411

Asia WGS AF: 0.426 AC: 1479 AN: 3478

EpiCase AF: 0.489

EpiControl AF: 0.492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	8.3
Dann	Benign	0.88

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: rs13959; hg19: chr9-75545882; COSMIC: COSV52789818;