9-72993844-T-C

Variant names:

• chr9-72993844-T-C
• rs1364451
• ENST00000419959.5:c.-14-40830A>G

Variant summary

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

The ENST00000419959.5(ALDH1A1):​c.-14-40830A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 151,706 control chromosomes in the GnomAD database, including 54,625 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 0.85 (54625 hom., cov: 32)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.764
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000419959.5	c.-14-40830A>G		intron_variant	Intron 1 of 7	5		ENSP00000388026.1
ALDH1A1	ENST00000446946.1	c.-14-40830A>G		intron_variant	Intron 1 of 6	5		ENSP00000401361.1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128148 AN: 151590 Hom.: 54588 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.881

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.845 AC: 128240 AN: 151706 Hom.: 54625 Cov.: 32 AF XY: 0.848 AC XY: 62848 AN XY: 74124

African (AFR) AF: 0.731 AC: 30264 AN: 41376

American (AMR) AF: 0.894 AC: 13639 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3032 AN: 3458

East Asian (EAS) AF: 0.960 AC: 4953 AN: 5160

South Asian (SAS) AF: 0.855 AC: 4116 AN: 4814

European-Finnish (FIN) AF: 0.886 AC: 9317 AN: 10510

Middle Eastern (MID) AF: 0.876 AC: 254 AN: 290

European-Non Finnish (NFE) AF: 0.885 AC: 60047 AN: 67836

Other (OTH) AF: 0.851 AC: 1781 AN: 2092

Alfa AF: 0.873 Hom.: 26479

Bravo AF: 0.842

Asia WGS AF: 0.893 AC: 3100 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.53
PhyloP100		-0.76

Splicing

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

Other links and lift over

dbSNP: rs1364451; hg19: chr9-75608760;