7-106251201-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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, single submitter B:1
• Conservation: PhyloP100: 1.19

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

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 534 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 534 AN: 152048 Hom.: 0 Cov.: 32

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.: 10 AF XY: 0.00450 AC XY: 606 AN XY: 134804

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.: 38 Cov.: 25 AF XY: 0.00474 AC XY: 3334 AN XY: 703944

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.: 0 Cov.: 32 AF XY: 0.00304 AC XY: 226 AN XY: 74424

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.: 4

Bravo AF: 0.00367

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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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

Other links and lift over

dbSNP: rs70937087; hg19: chr7-105891647;