NM_000689.5:c.1358+1596T>C

Variant names:

• chr9-72908006-A-G
• rs10781106
• NM_000689.5:c.1358+1596T>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.1358+1596T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,902 control chromosomes in the GnomAD database, including 14,977 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 (14977 hom., cov: 31)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 5 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=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.1358+1596T>C		intron_variant	Intron 11 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.1358+1596T>C		intron_variant	Intron 11 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64887 AN: 151784 Hom.: 14961 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.427 AC: 64929 AN: 151902 Hom.: 14977 Cov.: 31 AF XY: 0.431 AC XY: 32019 AN XY: 74228

African (AFR) AF: 0.239 AC: 9895 AN: 41434

American (AMR) AF: 0.487 AC: 7445 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1978 AN: 3468

East Asian (EAS) AF: 0.481 AC: 2480 AN: 5160

South Asian (SAS) AF: 0.585 AC: 2806 AN: 4800

European-Finnish (FIN) AF: 0.494 AC: 5202 AN: 10530

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33572 AN: 67936

Other (OTH) AF: 0.444 AC: 934 AN: 2104

Alfa AF: 0.487 Hom.: 7666

Bravo AF: 0.415

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-1.3
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: rs10781106; hg19: chr9-75522922;