rs2249978

Variant names:

• chr9-73012182-A-G
• rs2249978
• ENST00000419959.5:c.-14-59168T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-73012182-A-G
• chr9-73012182-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000419959.5(ALDH1A1):​c.-14-59168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,970 control chromosomes in the GnomAD database, including 27,548 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 0.58 (27548 hom., cov: 32)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000419959.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	ENST00000419959.5	TSL:5	c.-14-59168T>C		intron	N/A	ENSP00000388026.1
	ALDH1A1	ENST00000446946.1	TSL:5	c.-15+26359T>C		intron	N/A	ENSP00000401361.1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88457 AN: 151852 Hom.: 27540 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.582 AC: 88500 AN: 151970 Hom.: 27548 Cov.: 32 AF XY: 0.586 AC XY: 43565 AN XY: 74282

African (AFR) AF: 0.353 AC: 14607 AN: 41438

American (AMR) AF: 0.606 AC: 9238 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2203 AN: 3472

East Asian (EAS) AF: 0.458 AC: 2359 AN: 5152

South Asian (SAS) AF: 0.653 AC: 3146 AN: 4816

European-Finnish (FIN) AF: 0.763 AC: 8063 AN: 10574

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46747 AN: 67950

Other (OTH) AF: 0.615 AC: 1297 AN: 2108

Alfa AF: 0.617 Hom.: 3586

Bravo AF: 0.558

Asia WGS AF: 0.532 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2249978; hg19: chr9-75627098;