8-143575100-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_145201.6(NAPRT):c.1447-7C>G 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 0.0032 in 1,530,952 control chromosomes in the GnomAD database, including 108 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 0.014 (60 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (48 hom.)
• Consequence: NAPRT NM_145201.6 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.01593
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.260

Genes affected

NAPRT (HGNC:30450): (nicotinate phosphoribosyltransferase) Nicotinic acid (NA; niacin) is converted by nicotinic acid phosphoribosyltransferase (NAPRT; EC 2.4.2.11) to NA mononucleotide (NaMN), which is then converted to NA adenine dinucleotide (NaAD), and finally to nicotinamide adenine dinucleotide (NAD), which serves as a coenzyme in cellular redox reactions and is an essential component of a variety of processes in cellular metabolism including response to stress (Hara et al., 2007).[supplied by OMIM, Mar 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 8-143575100-G-C is Benign according to our data. Variant chr8-143575100-G-C is described in ClinVar as [Benign]. Clinvar id is 780130.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2101/152270) while in subpopulation AFR AF= 0.0454 (1886/41536). AF 95% confidence interval is 0.0437. There are 60 homozygotes in gnomad4. There are 979 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPRT	NM_145201.6	c.1447-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000449291.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPRT	ENST00000449291.7	c.1447-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_145201.6	P1
	ENST00000531730.1	n.430G>C		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2100 AN: 152152 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00739

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00427 AC: 625 AN: 146288 Hom.: 14 AF XY: 0.00353 AC XY: 274 AN XY: 77616

Gnomad AFR exome AF: 0.0472

Gnomad AMR exome AF: 0.00520

Gnomad ASJ exome AF: 0.00357

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000978

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00120

Gnomad OTH exome AF: 0.00398

GnomAD4 exome AF: 0.00203 AC: 2799 AN: 1378682 Hom.: 48 Cov.: 37 AF XY: 0.00195 AC XY: 1322 AN XY: 677136

Gnomad4 AFR exome AF: 0.0464

Gnomad4 AMR exome AF: 0.00575

Gnomad4 ASJ exome AF: 0.00466

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000646

Gnomad4 OTH exome AF: 0.00517

GnomAD4 genome AF: 0.0138 AC: 2101 AN: 152270 Hom.: 60 Cov.: 33 AF XY: 0.0131 AC XY: 979 AN XY: 74454

Gnomad4 AFR AF: 0.0454

Gnomad4 AMR AF: 0.00738

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00214 Hom.: 2

Bravo AF: 0.0162

Asia WGS AF: 0.00289 AC: 10 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

Jan 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.7
Dann	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.016
dbscSNV1_RF	Benign	0.15
SpliceAI score (max)		0.17		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: rs151207487; hg19: chr8-144657270;