9-72936384-C-T

Variant names:

• chr9-72936384-C-T
• rs2773806
• NM_000689.5:c.171+3764G>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.171+3764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,214 control chromosomes in the GnomAD database, including 61,905 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 0.90 (61905 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 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.171+3764G>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.171+3764G>A		intron	N/A	ENSP00000297785.3
	ALDH1A1	ENST00000419959.5	TSL:5	c.171+3764G>A		intron	N/A	ENSP00000388026.1
	ALDH1A1	ENST00000376939.5	TSL:5	c.171+3764G>A		intron	N/A	ENSP00000366138.1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136186 AN: 152096 Hom.: 61874 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.895 AC: 136274 AN: 152214 Hom.: 61905 Cov.: 32 AF XY: 0.897 AC XY: 66792 AN XY: 74438

African (AFR) AF: 0.723 AC: 30001 AN: 41490

American (AMR) AF: 0.947 AC: 14483 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2946 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5132 AN: 5178

South Asian (SAS) AF: 0.910 AC: 4392 AN: 4824

European-Finnish (FIN) AF: 0.970 AC: 10289 AN: 10608

Middle Eastern (MID) AF: 0.873 AC: 255 AN: 292

European-Non Finnish (NFE) AF: 0.969 AC: 65944 AN: 68034

Other (OTH) AF: 0.910 AC: 1922 AN: 2112

Alfa AF: 0.942 Hom.: 85991

Bravo AF: 0.885

Asia WGS AF: 0.933 AC: 3242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.71
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: rs2773806; hg19: chr9-75551300;