rs2305496

Positions:

• chr8-143577779-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145201.6(NAPRT):​c.354+37G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,574,126 control chromosomes in the GnomAD database, including 14,995 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 0.16 (2435 hom., cov: 33)
  • Exomes 𝑓: 0.12 (12560 hom.)
• Consequence: NAPRT NM_145201.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPRT	NM_145201.6	c.354+37G>T		intron_variant		ENST00000449291.7
NAPRT	NM_001286829.2	c.354+37G>T		intron_variant
NAPRT	NM_001363145.1	c.354+37G>T		intron_variant
NAPRT	NM_001363146.1	c.-215+37G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPRT	ENST00000449291.7	c.354+37G>T		intron_variant		1	NM_145201.6	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24410 AN: 152016 Hom.: 2438 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.169 AC: 29821 AN: 176260 Hom.: 3335 AF XY: 0.162 AC XY: 15802 AN XY: 97346

Gnomad AFR exome AF: 0.275

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.374

Gnomad SAS exome AF: 0.174

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.118 AC: 167850 AN: 1421992 Hom.: 12560 Cov.: 35 AF XY: 0.119 AC XY: 83992 AN XY: 704668

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.237

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0966

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.161 AC: 24423 AN: 152134 Hom.: 2435 Cov.: 33 AF XY: 0.161 AC XY: 11992 AN XY: 74386

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.142

Alfa AF: 0.131 Hom.: 274

Bravo AF: 0.171

Asia WGS AF: 0.245 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs2305496; hg19: chr8-144659949; COSMIC: COSV104373020; COSMIC: COSV104373020;