8-143574982-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate 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
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.084).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145201.6. 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
	NAPRT	NM_145201.6	MANE Select	c.1554+4G>C		splice_region intron	N/A	NP_660202.3
	NAPRT	NM_001286829.2		c.1515+4G>C		splice_region intron	N/A	NP_001273758.1	Q6XQN6-3
	NAPRT	NM_001363145.1		c.1473+4G>C		splice_region intron	N/A	NP_001350074.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPRT	ENST00000449291.7	TSL:1 MANE Select	c.1554+4G>C		splice_region intron	N/A	ENSP00000401508.2	Q6XQN6-1
	NAPRT	ENST00000426292.7	TSL:1	c.1515+4G>C		splice_region intron	N/A	ENSP00000390949.3	Q6XQN6-3
	NAPRT	ENST00000340490.7	TSL:1	n.1558G>C		non_coding_transcript_exon	Exon 12 of 12	ENSP00000341136.3	G5E977

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

GnomAD2 exomes AF: 0.0823 AC: 12015 AN: 146016 AF XY: 0.0868

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 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

African (AFR) AF: 0.0800 AC: 2522 AN: 31532

American (AMR) AF: 0.0438 AC: 1540 AN: 35128

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 1566 AN: 24364

East Asian (EAS) AF: 0.149 AC: 5322 AN: 35652

South Asian (SAS) AF: 0.133 AC: 10415 AN: 78062

European-Finnish (FIN) AF: 0.0689 AC: 3285 AN: 47654

Middle Eastern (MID) AF: 0.0761 AC: 431 AN: 5660

European-Non Finnish (NFE) AF: 0.0704 AC: 75603 AN: 1074482

Other (OTH) AF: 0.0790 AC: 4552 AN: 57644

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

African (AFR) AF: 0.0799 AC: 3318 AN: 41548

American (AMR) AF: 0.0558 AC: 855 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3472

East Asian (EAS) AF: 0.151 AC: 782 AN: 5170

South Asian (SAS) AF: 0.148 AC: 716 AN: 4826

European-Finnish (FIN) AF: 0.0694 AC: 737 AN: 10618

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0686 AC: 4669 AN: 68022

Other (OTH) AF: 0.0701 AC: 148 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Uncertain	0.99
PhyloP100		-0.49
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs77951814; hg19: chr8-144657152; COSMIC: COSV52783429; COSMIC: COSV52783429;