chr9-73034906-T-C

Variant names:

• chr9-73034906-T-C
• rs10869211
• ENST00000419959.5:c.-15+45461A>G

Variant summary

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

The ENST00000419959.5(ALDH1A1):​c.-15+45461A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,906 control chromosomes in the GnomAD database, including 24,005 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 0.56 (24005 hom., cov: 31)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 4 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 (NFE) allele frequency at 95% confidence interval = 0.603 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.-15+45461A>G		intron_variant	Intron 1 of 7	5		ENSP00000388026.1
ALDH1A1	ENST00000446946.1	c.-15+3635A>G		intron_variant	Intron 1 of 6	5		ENSP00000401361.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84307 AN: 151788 Hom.: 23985 Cov.: 31

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.555 AC: 84373 AN: 151906 Hom.: 24005 Cov.: 31 AF XY: 0.559 AC XY: 41459 AN XY: 74226

African (AFR) AF: 0.444 AC: 18406 AN: 41438

American (AMR) AF: 0.597 AC: 9100 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1743 AN: 3464

East Asian (EAS) AF: 0.414 AC: 2135 AN: 5162

South Asian (SAS) AF: 0.527 AC: 2533 AN: 4804

European-Finnish (FIN) AF: 0.687 AC: 7254 AN: 10560

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.608 AC: 41267 AN: 67924

Other (OTH) AF: 0.570 AC: 1199 AN: 2102

Alfa AF: 0.579 Hom.: 9994

Bravo AF: 0.543

Asia WGS AF: 0.465 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.78
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs10869211; hg19: chr9-75649822;