8-143574982-C-G

Variant names:

• chr8-143574982-C-G
• rs77951814
• NM_145201.6:c.1554+4G>C

Variant summary

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

The NM_145201.6(NAPRT):​c.1554+4G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 1,542,460 control chromosomes in the GnomAD database, including 4,888 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 0.076 (475 hom., cov: 34)
  • Exomes 𝑓: 0.076 (4413 hom.)
• Consequence: NAPRT NM_145201.6 splice_region, intron
• Scores: Splicing: ADA: 0.004719
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489

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

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 = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPRT	NM_145201.6	c.1554+4G>C		splice_region_variant, intron_variant	Intron 12 of 12	ENST00000449291.7	NP_660202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7	c.1554+4G>C		splice_region_variant, intron_variant	Intron 12 of 12	1	NM_145201.6	ENSP00000401508.2

Frequencies

GnomAD3 genomes AF: 0.0757 AC: 11517 AN: 152164 Hom.: 475 Cov.: 34

Gnomad AFR AF: 0.0799

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0559

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.0699

GnomAD3 exomes AF: 0.0823 AC: 12015 AN: 146016 Hom.: 580 AF XY: 0.0868 AC XY: 6714 AN XY: 77312

Gnomad AFR exome AF: 0.0789

Gnomad AMR exome AF: 0.0402

Gnomad ASJ exome AF: 0.0668

Gnomad EAS exome AF: 0.153

Gnomad SAS exome AF: 0.136

Gnomad FIN exome AF: 0.0735

Gnomad NFE exome AF: 0.0710

Gnomad OTH exome AF: 0.0860

GnomAD4 exome AF: 0.0757 AC: 105236 AN: 1390178 Hom.: 4413 Cov.: 33 AF XY: 0.0775 AC XY: 53058 AN XY: 684924

Gnomad4 AFR exome AF: 0.0800

Gnomad4 AMR exome AF: 0.0438

Gnomad4 ASJ exome AF: 0.0643

Gnomad4 EAS exome AF: 0.149

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.0689

Gnomad4 NFE exome AF: 0.0704

Gnomad4 OTH exome AF: 0.0790

GnomAD4 genome AF: 0.0757 AC: 11523 AN: 152282 Hom.: 475 Cov.: 34 AF XY: 0.0763 AC XY: 5680 AN XY: 74460

Gnomad4 AFR AF: 0.0799

Gnomad4 AMR AF: 0.0558

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.0686

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0469 Hom.: 60

Bravo AF: 0.0734

Asia WGS AF: 0.167 AC: 578 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	9.0
DANN	Uncertain	0.99

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0047
dbscSNV1_RF	Benign	0.11
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: rs77951814; hg19: chr8-144657152; COSMIC: COSV52783429; COSMIC: COSV52783429;