rs610529

Variant names:

• chr9-72918408-A-G
• rs610529
• NM_000689.5:c.850+312T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000689.5(ALDH1A1):​c.850+312T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,894 control chromosomes in the GnomAD database, including 14,308 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 (14308 hom., cov: 31)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.850+312T>C		intron_variant	Intron 8 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.850+312T>C		intron_variant	Intron 8 of 12	1	NM_000689.5	ENSP00000297785.3
ALDH1A1	ENST00000376939.5	c.678-1351T>C		intron_variant	Intron 7 of 7	5		ENSP00000366138.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65798 AN: 151774 Hom.: 14311 Cov.: 31

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.433 AC: 65811 AN: 151894 Hom.: 14308 Cov.: 31 AF XY: 0.430 AC XY: 31898 AN XY: 74236

African (AFR) AF: 0.424 AC: 17531 AN: 41386

American (AMR) AF: 0.447 AC: 6827 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3470

East Asian (EAS) AF: 0.526 AC: 2716 AN: 5166

South Asian (SAS) AF: 0.350 AC: 1691 AN: 4826

European-Finnish (FIN) AF: 0.413 AC: 4356 AN: 10536

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29953 AN: 67926

Other (OTH) AF: 0.448 AC: 945 AN: 2110

Alfa AF: 0.441 Hom.: 65442

Bravo AF: 0.440

Asia WGS AF: 0.471 AC: 1636 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.61
PhyloP100		0.062
Mutation Taster		=100/0	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: rs610529; hg19: chr9-75533324;