rs8187999

Positions:

• chr9-72900893-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000689.5(ALDH1A1):​c.*315G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 204,484 control chromosomes in the GnomAD database, including 54 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 0.019 (36 hom., cov: 32)
  • Exomes 𝑓: 0.024 (18 hom.)
• Consequence: ALDH1A1 NM_000689.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0191 (2901/152102) while in subpopulation SAS AF= 0.0332 (160/4818). AF 95% confidence interval is 0.029. There are 36 homozygotes in gnomad4. There are 1457 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2901 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDH1A1	NM_000689.5	c.*315G>C		3_prime_UTR_variant	13/13	ENST00000297785.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH1A1	ENST00000297785.8	c.*315G>C		3_prime_UTR_variant	13/13	1	NM_000689.5	P1

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2903 AN: 151984 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.00517

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.00938

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0168

GnomAD4 exome AF: 0.0237 AC: 1239 AN: 52382 Hom.: 18 Cov.: 0 AF XY: 0.0234 AC XY: 640 AN XY: 27392

Gnomad4 AFR exome AF: 0.00626

Gnomad4 AMR exome AF: 0.00874

Gnomad4 ASJ exome AF: 0.00826

Gnomad4 EAS exome AF: 0.0214

Gnomad4 SAS exome AF: 0.0374

Gnomad4 FIN exome AF: 0.0389

Gnomad4 NFE exome AF: 0.0256

Gnomad4 OTH exome AF: 0.0176

GnomAD4 genome AF: 0.0191 AC: 2901 AN: 152102 Hom.: 36 Cov.: 32 AF XY: 0.0196 AC XY: 1457 AN XY: 74340

Gnomad4 AFR AF: 0.00515

Gnomad4 AMR AF: 0.00936

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.0273

Gnomad4 SAS AF: 0.0332

Gnomad4 FIN AF: 0.0267

Gnomad4 NFE AF: 0.0272

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0241 Hom.: 31

Bravo AF: 0.0166

Asia WGS AF: 0.0310 AC: 107 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.1
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs8187999; hg19: chr9-75515809;