rs13959

Variant names:

• chr9-72930966-G-A
• rs13959
• NM_000689.5:c.225C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-72930966-G-A
• chr9-72930966-G-C
• chr9-72930966-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000689.5(ALDH1A1):​c.225C>T​(p.Ser75Ser) 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
• Publications: 43 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000689.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	NM_000689.5	MANE Select	c.225C>T	p.Ser75Ser	synonymous	Exon 3 of 13	NP_000680.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	ENST00000297785.8	TSL:1 MANE Select	c.225C>T	p.Ser75Ser	synonymous	Exon 3 of 13	ENSP00000297785.3	P00352
	ALDH1A1	ENST00000856212.1		c.315C>T	p.Ser105Ser	synonymous	Exon 4 of 14	ENSP00000526271.1
	ALDH1A1	ENST00000966555.1		c.294C>T	p.Ser98Ser	synonymous	Exon 4 of 14	ENSP00000636614.1

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

GnomAD2 exomes AF: 0.476 AC: 119437 AN: 250974 AF XY: 0.481

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 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

African (AFR) AF: 0.215 AC: 7181 AN: 33454

American (AMR) AF: 0.484 AC: 21645 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 11982 AN: 26128

East Asian (EAS) AF: 0.434 AC: 17224 AN: 39688

South Asian (SAS) AF: 0.490 AC: 42212 AN: 86224

European-Finnish (FIN) AF: 0.531 AC: 28348 AN: 53398

Middle Eastern (MID) AF: 0.393 AC: 2269 AN: 5768

European-Non Finnish (NFE) AF: 0.513 AC: 570457 AN: 1111736

Other (OTH) AF: 0.477 AC: 28802 AN: 60384

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

African (AFR) AF: 0.236 AC: 9795 AN: 41456

American (AMR) AF: 0.486 AC: 7412 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1553 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2359 AN: 5144

South Asian (SAS) AF: 0.487 AC: 2344 AN: 4818

European-Finnish (FIN) AF: 0.552 AC: 5812 AN: 10538

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.503 AC: 34194 AN: 67934

Other (OTH) AF: 0.434 AC: 917 AN: 2114

Alfa AF: 0.467 Hom.: 55819

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.3
DANN	Benign	0.88
PhyloP100		-1.5
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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