rs10487818

Variant names:

• chr7-106269615-A-T
• rs10487818
• NM_005746.3:c.448-303T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1692 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005746.3. 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
	NAMPT	NM_005746.3	MANE Select	c.448-303T>A		intron	N/A	NP_005737.1	P43490

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAMPT	ENST00000222553.8	TSL:1 MANE Select	c.448-303T>A		intron	N/A	ENSP00000222553.3	P43490
	NAMPT	ENST00000354289.9	TSL:1	c.448-303T>A		intron	N/A	ENSP00000346242.4	A0A0C4DFS8
	NAMPT	ENST00000968694.1		c.448-303T>A		intron	N/A	ENSP00000638753.1

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

African (AFR) AF: 0.00214 AC: 89 AN: 41584

American (AMR) AF: 0.00915 AC: 140 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0397 AC: 192 AN: 4832

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10628

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0143 AC: 970 AN: 68024

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	14
DANN	Benign	0.65
PhyloP100		2.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10487818; hg19: chr7-105910061;