ENST00000419959.5:c.-15+55178A>G

Variant names:

• chr9-73025189-T-C
• rs4745209
• ENST00000419959.5:c.-15+55178A>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+55178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,974 control chromosomes in the GnomAD database, including 7,935 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 0.31 (7935 hom., cov: 31)
• Consequence: ALDH1A1 ENST00000419959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	ENST00000419959.5	TSL:5	c.-15+55178A>G		intron	N/A	ENSP00000388026.1
	ALDH1A1	ENST00000446946.1	TSL:5	c.-15+13352A>G		intron	N/A	ENSP00000401361.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47798 AN: 151854 Hom.: 7927 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.315 AC: 47833 AN: 151974 Hom.: 7935 Cov.: 31 AF XY: 0.315 AC XY: 23372 AN XY: 74284

African (AFR) AF: 0.394 AC: 16304 AN: 41426

American (AMR) AF: 0.343 AC: 5226 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3468

East Asian (EAS) AF: 0.525 AC: 2705 AN: 5150

South Asian (SAS) AF: 0.309 AC: 1489 AN: 4818

European-Finnish (FIN) AF: 0.214 AC: 2264 AN: 10588

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17860 AN: 67950

Other (OTH) AF: 0.304 AC: 642 AN: 2112

Alfa AF: 0.287 Hom.: 20549

Bravo AF: 0.329

Asia WGS AF: 0.419 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs4745209; hg19: chr9-75640105;