Genetic Variant ENST00000424768.2:c.-389G>T (chr7-106285832-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000424768.2(NAMPT):c.-389G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0947 in 152,516 control chromosomes in the GnomAD database, including 930 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 0.095 ( 926 hom., cov: 32)

Exomes 𝑓: 0.16 ( 4 hom. )

Consequence

NAMPT
ENST00000424768.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.542

Publications

28 publications found

Variant links:

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]

NAMPT links:

NAMPT-AS1 (HGNC:56696): (NAMPT antisense RNA 1)

NAMPT-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
NAMPT	XM_047419699.1 link	c.-389G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	XP_047275655.1
NAMPT-AS1	NR_186647.1 link	n.587C>A	non_coding_transcript_exon_variant	Exon 1 of 1
NAMPT	XM_047419699.1 link	c.-389G>T	5_prime_UTR_variant	Exon 1 of 12	XP_047275655.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
NAMPT	ENST00000424768.2 link	c.-389G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	4	ENSP00000390591.2
NAMPT	ENST00000681255.1 link	c.-339G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12		ENSP00000506129.1
NAMPT-AS1	ENST00000609281.3 link	n.634C>A	non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.0946

AC:

14389

AN:

152024

Hom.:

926

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0245

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.0918

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0936

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.105

GnomAD4 exome

AF:

0.155

AC:

AN:

374

Hom.:

Cov.:

AF XY:

0.172

AC XY:

AN XY:

198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.172

AC:

AN:

332

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0945

AC:

14383

AN:

152142

Hom.:

926

Cov.:

AF XY:

0.0917

AC XY:

6820

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0245

AC:

1016

AN:

41508

American (AMR)

AF:

0.0916

AC:

1400

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

452

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0934

AC:

450

AN:

4816

European-Finnish (FIN)

AF:

0.101

AC:

1068

AN:

10574

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9597

AN:

67990

Other (OTH)

AF:

0.104

AC:

219

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

652

1305

1957

2610

3262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0786

Hom.:

325

Bravo

AF:

0.0918

Asia WGS

AF:

0.0330

AC:

113

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.9

(source)

DANN

Benign

0.63

PhyloP100

0.54

PromoterAI

0.011

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over