rs7043217

Variant names:

• chr9-72927979-G-A
• rs7043217
• NM_000689.5:c.443-802C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-72927979-G-A
• chr9-72927979-G-C
• chr9-72927979-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000689.5(ALDH1A1):​c.443-802C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 136,762 control chromosomes in the GnomAD database, including 14,401 homozygotes. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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 0.44 (14401 hom., cov: 24)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.704
• Publications: 10 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.443-802C>T		intron_variant	Intron 4 of 12	ENST00000297785.8	NP_000680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.443-802C>T		intron_variant	Intron 4 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.441 AC: 60242 AN: 136658 Hom.: 14396 Cov.: 24

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.406

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.441 AC: 60286 AN: 136762 Hom.: 14401 Cov.: 24 AF XY: 0.441 AC XY: 29166 AN XY: 66118

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.297 AC: 11547 AN: 38814

American (AMR) AF: 0.458 AC: 5951 AN: 12994

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 1906 AN: 3254

East Asian (EAS) AF: 0.418 AC: 1874 AN: 4488

South Asian (SAS) AF: 0.517 AC: 2115 AN: 4092

European-Finnish (FIN) AF: 0.503 AC: 4297 AN: 8546

Middle Eastern (MID) AF: 0.406 AC: 108 AN: 266

European-Non Finnish (NFE) AF: 0.507 AC: 31239 AN: 61630

Other (OTH) AF: 0.443 AC: 831 AN: 1874

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.503 Hom.: 21870

Bravo AF: 0.457

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.23
PhyloP100		0.70
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: rs7043217; hg19: chr9-75542895;