rs4730153

Positions:

• chr7-106263704-A-G

Variant summary

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

The NM_005746.3(NAMPT):​c.744-87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 967,860 control chromosomes in the GnomAD database, including 172,642 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 0.50 (22164 hom., cov: 32)
  • Exomes 𝑓: 0.60 (150478 hom.)
• Consequence: NAMPT NM_005746.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAMPT	NM_005746.3	c.744-87T>C		intron_variant		ENST00000222553.8
NAMPT	XM_047419700.1	c.*1449T>C		3_prime_UTR_variant	7/7
NAMPT	XM_047419699.1	c.744-87T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAMPT	ENST00000222553.8	c.744-87T>C		intron_variant		1	NM_005746.3	P4

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76520 AN: 151750 Hom.: 22147 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.520

GnomAD4 exome AF: 0.597 AC: 487407 AN: 815992 Hom.: 150478 AF XY: 0.600 AC XY: 255350 AN XY: 425692

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.744

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.899

Gnomad4 SAS exome AF: 0.649

Gnomad4 FIN exome AF: 0.672

Gnomad4 NFE exome AF: 0.575

Gnomad4 OTH exome AF: 0.570

GnomAD4 genome AF: 0.504 AC: 76559 AN: 151868 Hom.: 22164 Cov.: 32 AF XY: 0.519 AC XY: 38524 AN XY: 74232

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.524

Alfa AF: 0.510 Hom.: 3132

Bravo AF: 0.493

Asia WGS AF: 0.721 AC: 2508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.8
DANN	Benign	0.78

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: rs4730153; hg19: chr7-105904150;