rs2058539

Variant names:

• chr7-106276191-C-A
• rs2058539
• NM_005746.3:c.214+832G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-106276191-C-A
• chr7-106276191-C-G
• chr7-106276191-C-T

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+832G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,040 control chromosomes in the GnomAD database, including 29,127 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 0.61 (29127 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: NAMPT NM_005746.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.567
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

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.214+832G>T		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.214+832G>T		intron	N/A	ENSP00000222553.3	P43490
	NAMPT	ENST00000354289.9	TSL:1	c.214+832G>T		intron	N/A	ENSP00000346242.4	A0A0C4DFS8
	NAMPT	ENST00000968694.1		c.214+832G>T		intron	N/A	ENSP00000638753.1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93212 AN: 151922 Hom.: 29091 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.625

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: 0.614 AC: 93314 AN: 152040 Hom.: 29127 Cov.: 32 AF XY: 0.626 AC XY: 46484 AN XY: 74300

African (AFR) AF: 0.523 AC: 21670 AN: 41424

American (AMR) AF: 0.719 AC: 10975 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2090 AN: 3470

East Asian (EAS) AF: 0.892 AC: 4625 AN: 5184

South Asian (SAS) AF: 0.675 AC: 3256 AN: 4824

European-Finnish (FIN) AF: 0.710 AC: 7507 AN: 10576

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41119 AN: 67976

Other (OTH) AF: 0.629 AC: 1327 AN: 2110

Alfa AF: 0.557 Hom.: 3215

Bravo AF: 0.615

Asia WGS AF: 0.754 AC: 2623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.49
PhyloP100		0.57
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: rs2058539; hg19: chr7-105916637;