rs2305496

Variant names:

• chr8-143577779-C-A
• rs2305496
• NM_145201.6:c.354+37G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-143577779-C-A
• chr8-143577779-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145201.6(NAPRT):​c.354+37G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,574,126 control chromosomes in the GnomAD database, including 14,995 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 0.16 (2435 hom., cov: 33)
  • Exomes 𝑓: 0.12 (12560 hom.)
• Consequence: NAPRT NM_145201.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687
• Publications: 20 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPRT	NM_145201.6	c.354+37G>T		intron_variant	Intron 2 of 12	ENST00000449291.7	NP_660202.3
NAPRT	NM_001286829.2	c.354+37G>T		intron_variant	Intron 2 of 12		NP_001273758.1
NAPRT	NM_001363145.1	c.354+37G>T		intron_variant	Intron 2 of 11		NP_001350074.1
NAPRT	NM_001363146.1	c.-215+37G>T		intron_variant	Intron 2 of 11		NP_001350075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7	c.354+37G>T		intron_variant	Intron 2 of 12	1	NM_145201.6	ENSP00000401508.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24410 AN: 152016 Hom.: 2438 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.169 AC: 29821 AN: 176260 AF XY: 0.162

Gnomad AFR exome AF: 0.275

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.374

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.118 AC: 167850 AN: 1421992 Hom.: 12560 Cov.: 35 AF XY: 0.119 AC XY: 83992 AN XY: 704668

African (AFR) AF: 0.271 AC: 8838 AN: 32670

American (AMR) AF: 0.237 AC: 9220 AN: 38956

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 3103 AN: 25484

East Asian (EAS) AF: 0.344 AC: 12957 AN: 37672

South Asian (SAS) AF: 0.178 AC: 14711 AN: 82702

European-Finnish (FIN) AF: 0.111 AC: 5054 AN: 45676

Middle Eastern (MID) AF: 0.108 AC: 615 AN: 5712

European-Non Finnish (NFE) AF: 0.0966 AC: 105731 AN: 1094200

Other (OTH) AF: 0.129 AC: 7621 AN: 58920

GnomAD4 genome AF: 0.161 AC: 24423 AN: 152134 Hom.: 2435 Cov.: 33 AF XY: 0.161 AC XY: 11992 AN XY: 74386

African (AFR) AF: 0.260 AC: 10782 AN: 41512

American (AMR) AF: 0.136 AC: 2087 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3472

East Asian (EAS) AF: 0.358 AC: 1841 AN: 5148

South Asian (SAS) AF: 0.171 AC: 825 AN: 4814

European-Finnish (FIN) AF: 0.111 AC: 1172 AN: 10602

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.101 AC: 6872 AN: 67962

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.131 Hom.: 274

Bravo AF: 0.171

Asia WGS AF: 0.245 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		-0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2305496; hg19: chr8-144659949; COSMIC: COSV104373020; COSMIC: COSV104373020;