8-143575099-G-C

Variant names:

• chr8-143575099-G-C
• rs2290417
• NM_145201.6:c.1447-6C>G

Variant summary

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

The NM_145201.6(NAPRT):​c.1447-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,527,028 control chromosomes in the GnomAD database, including 383,794 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (34977 hom., cov: 33)
  • Exomes 𝑓: 0.71 (348817 hom.)
• Consequence: NAPRT NM_145201.6 splice_region, intron
• Scores: Splicing: ADA: 0.01841
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.650
• Publications: 17 publications found

Genes affected

NAPRT (HGNC:30450): (nicotinate phosphoribosyltransferase) Nicotinic acid (NA; niacin) is converted by nicotinic acid phosphoribosyltransferase (NAPRT; EC 2.4.2.11) to NA mononucleotide (NaMN), which is then converted to NA adenine dinucleotide (NaAD), and finally to nicotinamide adenine dinucleotide (NAD), which serves as a coenzyme in cellular redox reactions and is an essential component of a variety of processes in cellular metabolism including response to stress (Hara et al., 2007).[supplied by OMIM, Mar 2008]

ENSG00000255050 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPRT	NM_145201.6	c.1447-6C>G		splice_region_variant, intron_variant	Intron 11 of 12	ENST00000449291.7	NP_660202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7	c.1447-6C>G		splice_region_variant, intron_variant	Intron 11 of 12	1	NM_145201.6	ENSP00000401508.2

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102513 AN: 151982 Hom.: 34962 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.663

GnomAD2 exomes AF: 0.689 AC: 99278 AN: 144158 AF XY: 0.684

Gnomad AFR exome AF: 0.575

Gnomad AMR exome AF: 0.711

Gnomad ASJ exome AF: 0.620

Gnomad EAS exome AF: 0.740

Gnomad FIN exome AF: 0.664

Gnomad NFE exome AF: 0.726

Gnomad OTH exome AF: 0.679

GnomAD4 exome AF: 0.711 AC: 977131 AN: 1374928 Hom.: 348817 Cov.: 55 AF XY: 0.708 AC XY: 477915 AN XY: 674876

African (AFR) AF: 0.575 AC: 17888 AN: 31124

American (AMR) AF: 0.706 AC: 24164 AN: 34210

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 14396 AN: 23064

East Asian (EAS) AF: 0.714 AC: 25409 AN: 35564

South Asian (SAS) AF: 0.618 AC: 47181 AN: 76376

European-Finnish (FIN) AF: 0.661 AC: 31394 AN: 47488

Middle Eastern (MID) AF: 0.604 AC: 3350 AN: 5546

European-Non Finnish (NFE) AF: 0.727 AC: 773994 AN: 1064654

Other (OTH) AF: 0.692 AC: 39355 AN: 56902

GnomAD4 genome AF: 0.674 AC: 102581 AN: 152100 Hom.: 34977 Cov.: 33 AF XY: 0.671 AC XY: 49875 AN XY: 74342

African (AFR) AF: 0.583 AC: 24177 AN: 41462

American (AMR) AF: 0.707 AC: 10816 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2195 AN: 3470

East Asian (EAS) AF: 0.733 AC: 3782 AN: 5160

South Asian (SAS) AF: 0.603 AC: 2906 AN: 4822

European-Finnish (FIN) AF: 0.659 AC: 6991 AN: 10606

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49517 AN: 67964

Other (OTH) AF: 0.666 AC: 1407 AN: 2114

Alfa AF: 0.636 Hom.: 3890

Bravo AF: 0.673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.8
DANN	Benign	0.86
PhyloP100		0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.018
dbscSNV1_RF	Benign	0.068
SpliceAI score (max)		0.13		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: rs2290417; hg19: chr8-144657269;