9-72930224-G-T

Variant names:

• chr9-72930224-G-T
• rs4237255
• NM_000689.5:c.312+655C>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+655C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,890 control chromosomes in the GnomAD database, including 15,072 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 (15072 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	NM_000689.5	MANE Select	c.312+655C>A		intron	N/A	NP_000680.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	ENST00000297785.8	TSL:1 MANE Select	c.312+655C>A		intron	N/A	ENSP00000297785.3
	ALDH1A1	ENST00000419959.5	TSL:5	c.312+655C>A		intron	N/A	ENSP00000388026.1
	ALDH1A1	ENST00000376939.5	TSL:5	c.312+655C>A		intron	N/A	ENSP00000366138.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64921 AN: 151774 Hom.: 15064 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.428 AC: 64973 AN: 151890 Hom.: 15072 Cov.: 32 AF XY: 0.433 AC XY: 32153 AN XY: 74242

African (AFR) AF: 0.237 AC: 9823 AN: 41426

American (AMR) AF: 0.485 AC: 7401 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1548 AN: 3464

East Asian (EAS) AF: 0.458 AC: 2362 AN: 5162

South Asian (SAS) AF: 0.486 AC: 2341 AN: 4816

European-Finnish (FIN) AF: 0.551 AC: 5799 AN: 10530

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

European-Non Finnish (NFE) AF: 0.503 AC: 34184 AN: 67928

Other (OTH) AF: 0.434 AC: 917 AN: 2112

Alfa AF: 0.481 Hom.: 23278

Bravo AF: 0.411

Asia WGS AF: 0.419 AC: 1455 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.39
PhyloP100		-0.44
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: rs4237255; hg19: chr9-75545140;