chr9-73028919-T-C

Variant names:

• chr9-73028919-T-C
• rs7862749
• ENST00000419959.5:c.-15+51448A>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+51448A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,012 control chromosomes in the GnomAD database, including 31,842 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 0.64 (31842 hom., cov: 32)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 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+51448A>G		intron_variant	Intron 1 of 7	5		ENSP00000388026.1
ALDH1A1	ENST00000446946.1	c.-15+9622A>G		intron_variant	Intron 1 of 6	5		ENSP00000401361.1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97924 AN: 151892 Hom.: 31807 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.645 AC: 98017 AN: 152012 Hom.: 31842 Cov.: 32 AF XY: 0.648 AC XY: 48169 AN XY: 74322

African (AFR) AF: 0.574 AC: 23794 AN: 41442

American (AMR) AF: 0.668 AC: 10213 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2079 AN: 3464

East Asian (EAS) AF: 0.476 AC: 2458 AN: 5162

South Asian (SAS) AF: 0.652 AC: 3141 AN: 4818

European-Finnish (FIN) AF: 0.748 AC: 7902 AN: 10568

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46200 AN: 67960

Other (OTH) AF: 0.661 AC: 1394 AN: 2108

Alfa AF: 0.654 Hom.: 5110

Bravo AF: 0.634

Asia WGS AF: 0.566 AC: 1973 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.067
DANN	Benign	0.33
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs7862749; hg19: chr9-75643835;