chr9-72900893-C-G

Variant names:

• chr9-72900893-C-G
• rs8187999
• NM_000689.5:c.*315G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.65).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2901 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000689.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	NM_000689.5	MANE Select	c.*315G>C		3_prime_UTR	Exon 13 of 13	NP_000680.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A1	ENST00000297785.8	TSL:1 MANE Select	c.*315G>C		3_prime_UTR	Exon 13 of 13	ENSP00000297785.3	P00352
	ALDH1A1	ENST00000856212.1		c.*315G>C		3_prime_UTR	Exon 14 of 14	ENSP00000526271.1
	ALDH1A1	ENST00000966555.1		c.*315G>C		3_prime_UTR	Exon 14 of 14	ENSP00000636614.1

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

African (AFR) AF: 0.00626 AC: 12 AN: 1918

American (AMR) AF: 0.00874 AC: 30 AN: 3434

Ashkenazi Jewish (ASJ) AF: 0.00826 AC: 15 AN: 1816

East Asian (EAS) AF: 0.0214 AC: 92 AN: 4296

South Asian (SAS) AF: 0.0374 AC: 125 AN: 3340

European-Finnish (FIN) AF: 0.0389 AC: 67 AN: 1722

Middle Eastern (MID) AF: 0.0395 AC: 9 AN: 228

European-Non Finnish (NFE) AF: 0.0256 AC: 835 AN: 32554

Other (OTH) AF: 0.0176 AC: 54 AN: 3074

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

African (AFR) AF: 0.00515 AC: 214 AN: 41540

American (AMR) AF: 0.00936 AC: 143 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3470

East Asian (EAS) AF: 0.0273 AC: 141 AN: 5172

South Asian (SAS) AF: 0.0332 AC: 160 AN: 4818

European-Finnish (FIN) AF: 0.0267 AC: 283 AN: 10582

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0272 AC: 1845 AN: 67938

Other (OTH) AF: 0.0161 AC: 34 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.1
DANN	Benign	0.70
PhyloP100		-0.034
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=93/7	polymorphism

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: rs8187999; hg19: chr9-75515809;