9-72930154-A-T

Variant names:

• chr9-72930154-A-T
• rs348461
• NM_000689.5:c.312+725T>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.312+725T>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 152,068 control chromosomes in the GnomAD database, including 9,807 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 (9807 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 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.312+725T>A		intron	N/A	NP_000680.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	ENST00000297785.8	TSL:1 MANE Select	c.312+725T>A		intron	N/A	ENSP00000297785.3	P00352
	ALDH1A1	ENST00000856212.1		c.402+725T>A		intron	N/A	ENSP00000526271.1
	ALDH1A1	ENST00000966555.1		c.381+725T>A		intron	N/A	ENSP00000636614.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54162 AN: 151950 Hom.: 9810 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.365

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: 54178 AN: 152068 Hom.: 9807 Cov.: 32 AF XY: 0.355 AC XY: 26412 AN XY: 74326

African (AFR) AF: 0.319 AC: 13223 AN: 41480

American (AMR) AF: 0.381 AC: 5823 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1168 AN: 3472

East Asian (EAS) AF: 0.529 AC: 2737 AN: 5174

South Asian (SAS) AF: 0.363 AC: 1748 AN: 4810

European-Finnish (FIN) AF: 0.324 AC: 3433 AN: 10582

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

European-Non Finnish (NFE) AF: 0.365 AC: 24817 AN: 67968

Other (OTH) AF: 0.371 AC: 783 AN: 2112

Alfa AF: 0.350 Hom.: 1261

Bravo AF: 0.361

Asia WGS AF: 0.463 AC: 1606 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.59
PhyloP100		0.26
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: rs348461; hg19: chr9-75545070;