chr8-143578087-G-T

Variant names:

• chr8-143578087-G-T
• rs2015562
• NM_145201.6:c.226+6C>A

Variant summary

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

The NM_145201.6(NAPRT):​c.226+6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,517,890 control chromosomes in the GnomAD database, including 15,805 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (3418 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12387 hom.)
• Consequence: NAPRT NM_145201.6 splice_region, intron
• Scores: Splicing: ADA: 0.0001474
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925
• Publications: 18 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAPRT	NM_145201.6	c.226+6C>A		splice_region_variant, intron_variant	Intron 1 of 12	ENST00000449291.7	NP_660202.3
NAPRT	NM_001286829.2	c.226+6C>A		splice_region_variant, intron_variant	Intron 1 of 12		NP_001273758.1
NAPRT	NM_001363145.1	c.226+6C>A		splice_region_variant, intron_variant	Intron 1 of 11		NP_001350074.1
NAPRT	NM_001363146.1	c.-343+6C>A		splice_region_variant, intron_variant	Intron 1 of 11		NP_001350075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAPRT	ENST00000449291.7	c.226+6C>A		splice_region_variant, intron_variant	Intron 1 of 12	1	NM_145201.6	ENSP00000401508.2

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27798 AN: 151630 Hom.: 3413 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.182 AC: 25159 AN: 138478 AF XY: 0.170

Gnomad AFR exome AF: 0.374

Gnomad AMR exome AF: 0.281

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.374

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.117 AC: 159795 AN: 1366146 Hom.: 12387 Cov.: 34 AF XY: 0.117 AC XY: 79155 AN XY: 673712

African (AFR) AF: 0.353 AC: 10520 AN: 29804

American (AMR) AF: 0.250 AC: 7758 AN: 31080

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 2688 AN: 22022

East Asian (EAS) AF: 0.337 AC: 12245 AN: 36322

South Asian (SAS) AF: 0.168 AC: 12863 AN: 76554

European-Finnish (FIN) AF: 0.110 AC: 4121 AN: 37446

Middle Eastern (MID) AF: 0.114 AC: 500 AN: 4390

European-Non Finnish (NFE) AF: 0.0949 AC: 101713 AN: 1072122

Other (OTH) AF: 0.131 AC: 7387 AN: 56406

GnomAD4 genome AF: 0.183 AC: 27835 AN: 151744 Hom.: 3418 Cov.: 32 AF XY: 0.184 AC XY: 13657 AN XY: 74168

African (AFR) AF: 0.336 AC: 13886 AN: 41300

American (AMR) AF: 0.171 AC: 2611 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3466

East Asian (EAS) AF: 0.345 AC: 1761 AN: 5106

South Asian (SAS) AF: 0.161 AC: 772 AN: 4808

European-Finnish (FIN) AF: 0.111 AC: 1173 AN: 10558

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0997 AC: 6767 AN: 67904

Other (OTH) AF: 0.154 AC: 325 AN: 2114

Alfa AF: 0.131 Hom.: 923

Bravo AF: 0.198

Asia WGS AF: 0.237 AC: 823 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.93
PromoterAI		0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.086
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: rs2015562; hg19: chr8-144660257;