chr7-106249610-A-G

Variant names:

• chr7-106249610-A-G
• rs9034
• NM_005746.3:c.*1473T>C

Variant summary

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

The NM_005746.3(NAMPT):​c.*1473T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,770 control chromosomes in the GnomAD database, including 32,062 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 0.65 (32062 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: NAMPT NM_005746.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08
• Publications: 11 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAMPT	NM_005746.3	c.*1473T>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000222553.8	NP_005737.1
NAMPT	XM_047419699.1	c.*1473T>C		3_prime_UTR_variant	Exon 12 of 12		XP_047275655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAMPT	ENST00000222553.8	c.*1473T>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_005746.3	ENSP00000222553.3

Frequencies

GnomAD3 genomes AF: 0.646 AC: 97950 AN: 151652 Hom.: 32024 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.658

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: 0.646 AC: 98054 AN: 151770 Hom.: 32062 Cov.: 31 AF XY: 0.658 AC XY: 48769 AN XY: 74166

African (AFR) AF: 0.577 AC: 23874 AN: 41372

American (AMR) AF: 0.739 AC: 11243 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2187 AN: 3468

East Asian (EAS) AF: 0.911 AC: 4711 AN: 5174

South Asian (SAS) AF: 0.694 AC: 3344 AN: 4818

European-Finnish (FIN) AF: 0.738 AC: 7790 AN: 10552

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42767 AN: 67870

Other (OTH) AF: 0.661 AC: 1391 AN: 2104

Alfa AF: 0.621 Hom.: 6166

Bravo AF: 0.647

Asia WGS AF: 0.776 AC: 2701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.20
PhyloP100		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs9034; hg19: chr7-105890056;