9-72938037-C-G

Variant names:

• chr9-72938037-C-G
• rs1330286
• NM_000689.5:c.171+2111G>C

Variant summary

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

The NM_000689.5(ALDH1A1):​c.171+2111G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 151,882 control chromosomes in the GnomAD database, including 27,570 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 0.59 (27570 hom., cov: 31)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• Publications: 15 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.171+2111G>C		intron_variant	Intron 2 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.171+2111G>C		intron_variant	Intron 2 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90138 AN: 151764 Hom.: 27558 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.594 AC: 90194 AN: 151882 Hom.: 27570 Cov.: 31 AF XY: 0.597 AC XY: 44327 AN XY: 74212

African (AFR) AF: 0.446 AC: 18455 AN: 41392

American (AMR) AF: 0.604 AC: 9216 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1956 AN: 3468

East Asian (EAS) AF: 0.446 AC: 2289 AN: 5138

South Asian (SAS) AF: 0.574 AC: 2754 AN: 4800

European-Finnish (FIN) AF: 0.750 AC: 7903 AN: 10538

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45491 AN: 67970

Other (OTH) AF: 0.607 AC: 1277 AN: 2104

Alfa AF: 0.527 Hom.: 1597

Bravo AF: 0.574

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.39
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1330286; hg19: chr9-75552953;