rs2058540

Variant names:

• chr7-106276262-T-C
• rs2058540
• NM_005746.3:c.214+761A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005746.3(NAMPT):​c.214+761A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,134 control chromosomes in the GnomAD database, including 7,001 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 0.28 (7001 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: NAMPT NM_005746.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAMPT	NM_005746.3	c.214+761A>G		intron_variant	Intron 2 of 10	ENST00000222553.8	NP_005737.1
NAMPT	XM_047419699.1	c.214+761A>G		intron_variant	Intron 3 of 11		XP_047275655.1
NAMPT	XM_047419700.1	c.214+761A>G		intron_variant	Intron 2 of 6		XP_047275656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAMPT	ENST00000222553.8	c.214+761A>G		intron_variant	Intron 2 of 10	1	NM_005746.3	ENSP00000222553.3

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42343 AN: 152016 Hom.: 6993 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.274

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.278 AC: 42355 AN: 152134 Hom.: 7001 Cov.: 32 AF XY: 0.288 AC XY: 21383 AN XY: 74348

African (AFR) AF: 0.0989 AC: 4111 AN: 41550

American (AMR) AF: 0.337 AC: 5147 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 895 AN: 3466

East Asian (EAS) AF: 0.408 AC: 2107 AN: 5160

South Asian (SAS) AF: 0.456 AC: 2198 AN: 4818

European-Finnish (FIN) AF: 0.385 AC: 4066 AN: 10574

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22807 AN: 67970

Other (OTH) AF: 0.273 AC: 576 AN: 2108

Alfa AF: 0.299 Hom.: 1204

Bravo AF: 0.267

Asia WGS AF: 0.369 AC: 1286 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.73
PhyloP100		0.040
Mutation Taster		=100/0	polymorphism (auto)

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: rs2058540; hg19: chr7-105916708;