rs2017362

Variant names:

• chr9-72929475-C-T
• rs2017362
• NM_000689.5:c.313-454G>A

Variant summary

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

The NM_000689.5(ALDH1A1):​c.313-454G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,060 control chromosomes in the GnomAD database, including 9,789 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 0.36 (9789 hom., cov: 33)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.313-454G>A		intron_variant	Intron 3 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.313-454G>A		intron_variant	Intron 3 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54111 AN: 151942 Hom.: 9792 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.356 AC: 54127 AN: 152060 Hom.: 9789 Cov.: 33 AF XY: 0.355 AC XY: 26385 AN XY: 74332

African (AFR) AF: 0.318 AC: 13182 AN: 41494

American (AMR) AF: 0.381 AC: 5821 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1167 AN: 3468

East Asian (EAS) AF: 0.530 AC: 2733 AN: 5160

South Asian (SAS) AF: 0.363 AC: 1749 AN: 4818

European-Finnish (FIN) AF: 0.324 AC: 3422 AN: 10570

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24825 AN: 67970

Other (OTH) AF: 0.370 AC: 783 AN: 2114

Alfa AF: 0.366 Hom.: 15965

Bravo AF: 0.361

Asia WGS AF: 0.464 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.31
PhyloP100		-0.36
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: rs2017362; hg19: chr9-75544391;