9-72950038-C-T

Variant names:

• chr9-72950038-C-T
• rs8187876
• NM_000689.5:c.66+2897G>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.66+2897G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 151,410 control chromosomes in the GnomAD database, including 2,383 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 0.14 (2383 hom., cov: 30)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 13 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 (EAS) allele frequency at 95% confidence interval = 0.459 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.66+2897G>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.66+2897G>A		intron	N/A	ENSP00000297785.3	P00352
	ALDH1A1	ENST00000856212.1		c.156+2067G>A		intron	N/A	ENSP00000526271.1
	ALDH1A1	ENST00000966555.1		c.135+1765G>A		intron	N/A	ENSP00000636614.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21592 AN: 151290 Hom.: 2373 Cov.: 30

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0565

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.143 AC: 21633 AN: 151410 Hom.: 2383 Cov.: 30 AF XY: 0.149 AC XY: 11011 AN XY: 73952

African (AFR) AF: 0.225 AC: 9295 AN: 41312

American (AMR) AF: 0.206 AC: 3123 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 459 AN: 3458

East Asian (EAS) AF: 0.475 AC: 2439 AN: 5136

South Asian (SAS) AF: 0.228 AC: 1099 AN: 4810

European-Finnish (FIN) AF: 0.101 AC: 1058 AN: 10482

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0565 AC: 3830 AN: 67744

Other (OTH) AF: 0.136 AC: 286 AN: 2108

Alfa AF: 0.0881 Hom.: 4987

Bravo AF: 0.156

Asia WGS AF: 0.337 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.62
PhyloP100		-1.4
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: rs8187876; hg19: chr9-75564954;