rs41430346

chr7-106272709-C-Gchr7-106272709-C-T

Variant summary

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

The NM_005746.3(NAMPT):c.319-51G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,594,120 control chromosomes in the GnomAD database, including 423 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 0.028 (91 hom., cov: 32)
  • Exomes 𝑓: 0.018 (332 hom.)
• Consequence: NAMPT NM_005746.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125

Genes affected

NAMPT (HGNC:30092): (nicotinamide phosphoribosyltransferase) This gene encodes a protein that catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, one step in the biosynthesis of nicotinamide adenine dinucleotide. The protein belongs to the nicotinic acid phosphoribosyltransferase (NAPRTase) family and is thought to be involved in many important biological processes, including metabolism, stress response and aging. This gene has a pseudogene on chromosome 10. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAMPT	NM_005746.3	c.319-51G>C		intron_variant		ENST00000222553.8
NAMPT	XM_047419699.1	c.319-51G>C		intron_variant
NAMPT	XM_047419700.1	c.319-51G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAMPT	ENST00000222553.8	c.319-51G>C		intron_variant		1	NM_005746.3	P4

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4187 AN: 152092 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.00443

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0195 AC: 4770 AN: 245078 Hom.: 84 AF XY: 0.0185 AC XY: 2468 AN XY: 133062

Gnomad AFR exome AF: 0.0622

Gnomad AMR exome AF: 0.0168

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.0162

Gnomad SAS exome AF: 0.00982

Gnomad FIN exome AF: 0.00546

Gnomad NFE exome AF: 0.0197

Gnomad OTH exome AF: 0.0266

GnomAD4 exome AF: 0.0184 AC: 26585 AN: 1441910 Hom.: 332 Cov.: 26 AF XY: 0.0181 AC XY: 12991 AN XY: 718200

Gnomad4 AFR exome AF: 0.0621

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.0131

Gnomad4 SAS exome AF: 0.0107

Gnomad4 FIN exome AF: 0.00602

Gnomad4 NFE exome AF: 0.0184

Gnomad4 OTH exome AF: 0.0212

GnomAD4 genome AF: 0.0275 AC: 4190 AN: 152210 Hom.: 91 Cov.: 32 AF XY: 0.0264 AC XY: 1966 AN XY: 74432

Gnomad4 AFR AF: 0.0585

Gnomad4 AMR AF: 0.0189

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.0170

Gnomad4 SAS AF: 0.00994

Gnomad4 FIN AF: 0.00443

Gnomad4 NFE AF: 0.0170

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0229 Hom.: 15

Bravo AF: 0.0299

Asia WGS AF: 0.0230 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.9
Dann	Benign	0.47

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: rs41430346; hg19: chr7-105913155;