rs348449

Variant names:

• chr9-72940066-G-A
• rs348449
• NM_000689.5:c.171+82C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-72940066-G-A
• chr9-72940066-G-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+82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 987,102 control chromosomes in the GnomAD database, including 454,441 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 0.94 (66769 hom., cov: 26)
  • Exomes 𝑓: 0.96 (387672 hom.)
• Consequence: ALDH1A1 NM_000689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A1	NM_000689.5	c.171+82C>T		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+82C>T		intron_variant	Intron 2 of 12	1	NM_000689.5	ENSP00000297785.3

Frequencies

GnomAD3 genomes AF: 0.938 AC: 141849 AN: 151202 Hom.: 66719 Cov.: 26

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.945

GnomAD4 exome AF: 0.963 AC: 804688 AN: 835786 Hom.: 387672 AF XY: 0.961 AC XY: 418244 AN XY: 435082

African (AFR) AF: 0.856 AC: 16965 AN: 19820

American (AMR) AF: 0.980 AC: 35039 AN: 35762

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 19890 AN: 20314

East Asian (EAS) AF: 0.959 AC: 34330 AN: 35780

South Asian (SAS) AF: 0.925 AC: 60537 AN: 65470

European-Finnish (FIN) AF: 0.975 AC: 43953 AN: 45074

Middle Eastern (MID) AF: 0.957 AC: 4191 AN: 4380

European-Non Finnish (NFE) AF: 0.969 AC: 552576 AN: 570288

Other (OTH) AF: 0.957 AC: 37207 AN: 38898

GnomAD4 genome AF: 0.938 AC: 141959 AN: 151316 Hom.: 66769 Cov.: 26 AF XY: 0.939 AC XY: 69344 AN XY: 73854

African (AFR) AF: 0.861 AC: 35386 AN: 41122

American (AMR) AF: 0.966 AC: 14666 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3392 AN: 3470

East Asian (EAS) AF: 0.960 AC: 4906 AN: 5108

South Asian (SAS) AF: 0.931 AC: 4460 AN: 4790

European-Finnish (FIN) AF: 0.980 AC: 10179 AN: 10392

Middle Eastern (MID) AF: 0.945 AC: 276 AN: 292

European-Non Finnish (NFE) AF: 0.969 AC: 65801 AN: 67936

Other (OTH) AF: 0.946 AC: 1992 AN: 2106

Alfa AF: 0.960 Hom.: 86561

Bravo AF: 0.934

Asia WGS AF: 0.930 AC: 3235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.22
PhyloP100		-0.75
Mutation Taster		=17/83	disease causing

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: rs348449; hg19: chr9-75554982;