Variant 7-106251201-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005746.3(NAMPT):c.1366-8T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,560,756 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 38 hom. )

Consequence

NAMPT
NM_005746.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002130

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.19

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-106251201-A-G is Benign according to our data. Variant chr7-106251201-A-G is described in ClinVar as [Benign]. Clinvar id is 719384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 532 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAMPT	NM_005746.3 linkuse as main transcript	c.1366-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000222553.8	NP_005737.1
NAMPT	XM_047419699.1 linkuse as main transcript	c.1366-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_047275655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAMPT	ENST00000222553.8 linkuse as main transcript	c.1366-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005746.3	ENSP00000222553	P4

Frequencies

GnomAD3 genomes

AF:

0.00351

AC:

534

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.0303

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00464

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00447

AC:

1114

AN:

249310

Hom.:

AF XY:

0.00450

AC XY:

606

AN XY:

134804

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.00353

Gnomad ASJ exome

AF:

0.0276

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00254

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00507

Gnomad OTH exome

AF:

0.00592

GnomAD4 exome

AF:

0.00470

AC:

6626

AN:

1408590

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

3334

AN XY:

703944

show subpopulations

Gnomad4 AFR exome

AF:

0.000744

Gnomad4 AMR exome

AF:

0.00377

Gnomad4 ASJ exome

AF:

0.0277

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00213

Gnomad4 FIN exome

AF:

0.00117

Gnomad4 NFE exome

AF:

0.00484

Gnomad4 OTH exome

AF:

0.00499

GnomAD4 genome

AF:

0.00350

AC:

532

AN:

152166

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

226

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.00295

Gnomad4 ASJ

AF:

0.0303

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00464

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00588

Hom.:

Bravo

AF:

0.00367

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.7

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over