9-72944933-T-C

Variant names:

• chr9-72944933-T-C
• rs8187890
• NM_000689.5:c.67-4681A>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.67-4681A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,094 control chromosomes in the GnomAD database, including 978 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 0.10 (978 hom., cov: 32)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 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.67-4681A>G		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.67-4681A>G		intron	N/A	ENSP00000297785.3
	ALDH1A1	ENST00000419959.5	TSL:5	c.67-4681A>G		intron	N/A	ENSP00000388026.1
	ALDH1A1	ENST00000376939.5	TSL:5	c.67-4681A>G		intron	N/A	ENSP00000366138.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15295 AN: 151976 Hom.: 975 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0673

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.101 AC: 15317 AN: 152094 Hom.: 978 Cov.: 32 AF XY: 0.0986 AC XY: 7330 AN XY: 74376

African (AFR) AF: 0.181 AC: 7491 AN: 41490

American (AMR) AF: 0.0671 AC: 1023 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5180

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4824

European-Finnish (FIN) AF: 0.0918 AC: 974 AN: 10608

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0770 AC: 5236 AN: 67964

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.0786 Hom.: 1019

Bravo AF: 0.103

Asia WGS AF: 0.0310 AC: 110 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	19
DANN	Benign	0.86
PhyloP100		3.1
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: rs8187890; hg19: chr9-75559849;