rs10487818

Positions:

• chr7-106269615-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005746.3(NAMPT):​c.448-303T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 152,346 control chromosomes in the GnomAD database, including 16 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 0.011 (16 hom., cov: 32)
• Consequence: NAMPT NM_005746.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63

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=-0.87).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0111 (1692/152346) while in subpopulation SAS AF= 0.0397 (192/4832). AF 95% confidence interval is 0.0351. There are 16 homozygotes in gnomad4. There are 886 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1692 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAMPT	NM_005746.3	c.448-303T>A		intron_variant		ENST00000222553.8
NAMPT	XM_047419699.1	c.448-303T>A		intron_variant
NAMPT	XM_047419700.1	c.448-303T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAMPT	ENST00000222553.8	c.448-303T>A		intron_variant		1	NM_005746.3	P4

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1697 AN: 152228 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0407

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0111 AC: 1692 AN: 152346 Hom.: 16 Cov.: 32 AF XY: 0.0119 AC XY: 886 AN XY: 74512

Gnomad4 AFR AF: 0.00214

Gnomad4 AMR AF: 0.00915

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0397

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0147 Hom.: 1

Bravo AF: 0.00993

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	14
DANN	Benign	0.65

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: rs10487818; hg19: chr7-105910061;