8-143578019-A-G

Position:

• chr8-143578019-A-G

Variant summary

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

The NM_145201.6(NAPRT):​c.226+74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,520,020 control chromosomes in the GnomAD database, including 353,471 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.68 (34885 hom., cov: 26)
  • Exomes 𝑓: 0.68 (318586 hom.)
• Consequence: NAPRT NM_145201.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.01

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: This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPRT	NM_145201.6	c.226+74T>C		intron_variant		ENST00000449291.7
NAPRT	NM_001286829.2	c.226+74T>C		intron_variant
NAPRT	NM_001363145.1	c.226+74T>C		intron_variant
NAPRT	NM_001363146.1	c.-343+74T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPRT	ENST00000449291.7	c.226+74T>C		intron_variant		1	NM_145201.6	P1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 102202 AN: 150124 Hom.: 34858 Cov.: 26

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.681 AC: 933028 AN: 1369782 Hom.: 318586 Cov.: 26 AF XY: 0.679 AC XY: 458426 AN XY: 675188

Gnomad4 AFR exome AF: 0.660

Gnomad4 AMR exome AF: 0.701

Gnomad4 ASJ exome AF: 0.657

Gnomad4 EAS exome AF: 0.718

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.657

Gnomad4 NFE exome AF: 0.686

Gnomad4 OTH exome AF: 0.678

GnomAD4 genome AF: 0.681 AC: 102283 AN: 150238 Hom.: 34885 Cov.: 26 AF XY: 0.679 AC XY: 49833 AN XY: 73360

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.677

Alfa AF: 0.580 Hom.: 1626

Bravo AF: 0.682

Asia WGS AF: 0.633 AC: 2205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.16
BranchPoint Hunter		0.0

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: rs896953; hg19: chr8-144660189; COSMIC: COSV52787017; COSMIC: COSV52787017;