NM_000689.5:c.312+157T>G

Variant names:

• chr9-72930722-A-C
• rs3815836
• NM_000689.5:c.312+157T>G

Variant summary

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

The NM_000689.5(ALDH1A1):​c.312+157T>G 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 151,938 control chromosomes in the GnomAD database, including 15,045 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 (15045 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• Publications: 8 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=-0.87).
• 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 rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.312+157T>G		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.312+157T>G		intron_variant	Intron 3 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64858 AN: 151820 Hom.: 15037 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.427 AC: 64909 AN: 151938 Hom.: 15045 Cov.: 32 AF XY: 0.433 AC XY: 32118 AN XY: 74248

African (AFR) AF: 0.236 AC: 9786 AN: 41462

American (AMR) AF: 0.485 AC: 7407 AN: 15266

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

East Asian (EAS) AF: 0.457 AC: 2360 AN: 5162

South Asian (SAS) AF: 0.486 AC: 2335 AN: 4808

European-Finnish (FIN) AF: 0.550 AC: 5797 AN: 10538

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34167 AN: 67928

Other (OTH) AF: 0.431 AC: 907 AN: 2102

Alfa AF: 0.478 Hom.: 29457

Bravo AF: 0.411

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.39
PhyloP100		-0.41
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: rs3815836; hg19: chr9-75545638; COSMIC: COSV52793500;