ENST00000449759.2:c.-78-3081C>T

Variant names:

• chr16-29676039-C-T
• rs3862476
• ENST00000449759.2:c.-78-3081C>T

Variant summary

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

The ENST00000449759.2(QPRT):​c.-78-3081C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 152,170 control chromosomes in the GnomAD database, including 68,829 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 0.95 (68829 hom., cov: 30)
• Consequence: QPRT ENST00000449759.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• Publications: 7 publications found

Genes affected

QPRT (HGNC:9755): (quinolinate phosphoribosyltransferase) This gene encodes a key enzyme in catabolism of quinolinate, an intermediate in the tryptophan-nicotinamide adenine dinucleotide pathway. Quinolinate acts as a most potent endogenous exitotoxin to neurons. Elevation of quinolinate levels in the brain has been linked to the pathogenesis of neurodegenerative disorders such as epilepsy, Alzheimer's disease, and Huntington's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000449759.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QPRT	ENST00000449759.2	TSL:3	c.-78-3081C>T		intron	N/A	ENSP00000404873.3	Q15274

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144542 AN: 152052 Hom.: 68771 Cov.: 30

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.951 AC: 144659 AN: 152170 Hom.: 68829 Cov.: 30 AF XY: 0.951 AC XY: 70715 AN XY: 74386

African (AFR) AF: 0.986 AC: 40949 AN: 41530

American (AMR) AF: 0.964 AC: 14709 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3243 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5184

South Asian (SAS) AF: 0.959 AC: 4621 AN: 4818

European-Finnish (FIN) AF: 0.923 AC: 9770 AN: 10584

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63100 AN: 68014

Other (OTH) AF: 0.957 AC: 2020 AN: 2110

Alfa AF: 0.933 Hom.: 129140

Bravo AF: 0.955

Asia WGS AF: 0.986 AC: 3428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.97
DANN	Benign	0.78
PhyloP100		-0.41

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: rs3862476; hg19: chr16-29687360;