Variant 8-143575100-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.260

Variant links:

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]

NAPRT links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPRT	NM_145201.6 linkuse as main transcript	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 linkuse as main transcript	c.1447-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_145201.6	P1	Q6XQN6-1
	ENST00000531730.1 linkuse as main transcript	n.430G>C		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2100

AN:

152152

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00353

AC XY:

274

AN XY:

77616

show subpopulations

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.:

Cov.:

AF XY:

0.00195

AC XY:

1322

AN XY:

677136

show subpopulations

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.:

Cov.:

AF XY:

0.0131

AC XY:

979

AN XY:

74454

show subpopulations

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.:

Bravo

AF:

0.0162

Asia WGS

AF:

0.00289

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	Jan 19, 2018	- -

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

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