rs896953

Variant names:

• chr8-143578019-A-G
• rs896953
• NM_145201.6:c.226+74T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-143578019-A-G
• chr8-143578019-A-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.226+74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,520,020 control chromosomes in the GnomAD database, including 353,471 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.68 (34885 hom., cov: 26)
  • Exomes 𝑓: 0.68 (318586 hom.)
• Consequence: NAPRT NM_145201.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.01
• Publications: 10 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145201.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPRT	NM_145201.6	MANE Select	c.226+74T>C		intron	N/A	NP_660202.3
	NAPRT	NM_001286829.2		c.226+74T>C		intron	N/A	NP_001273758.1
	NAPRT	NM_001363145.1		c.226+74T>C		intron	N/A	NP_001350074.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPRT	ENST00000449291.7	TSL:1 MANE Select	c.226+74T>C		intron	N/A	ENSP00000401508.2
	NAPRT	ENST00000426292.7	TSL:1	c.226+74T>C		intron	N/A	ENSP00000390949.3
	NAPRT	ENST00000340490.7	TSL:1	n.226+74T>C		intron	N/A	ENSP00000341136.3

Frequencies

GnomAD3 genomes AF: 0.681 AC: 102202 AN: 150124 Hom.: 34858 Cov.: 26

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.681 AC: 933028 AN: 1369782 Hom.: 318586 Cov.: 26 AF XY: 0.679 AC XY: 458426 AN XY: 675188

African (AFR) AF: 0.660 AC: 20342 AN: 30800

American (AMR) AF: 0.701 AC: 26148 AN: 37296

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 14338 AN: 21834

East Asian (EAS) AF: 0.718 AC: 27222 AN: 37890

South Asian (SAS) AF: 0.611 AC: 47194 AN: 77204

European-Finnish (FIN) AF: 0.657 AC: 27461 AN: 41796

Middle Eastern (MID) AF: 0.678 AC: 3174 AN: 4684

European-Non Finnish (NFE) AF: 0.686 AC: 728752 AN: 1061654

Other (OTH) AF: 0.678 AC: 38397 AN: 56624

GnomAD4 genome AF: 0.681 AC: 102283 AN: 150238 Hom.: 34885 Cov.: 26 AF XY: 0.679 AC XY: 49833 AN XY: 73360

African (AFR) AF: 0.660 AC: 27010 AN: 40932

American (AMR) AF: 0.706 AC: 10728 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2285 AN: 3450

East Asian (EAS) AF: 0.736 AC: 3699 AN: 5024

South Asian (SAS) AF: 0.606 AC: 2838 AN: 4680

European-Finnish (FIN) AF: 0.662 AC: 6852 AN: 10348

Middle Eastern (MID) AF: 0.656 AC: 189 AN: 288

European-Non Finnish (NFE) AF: 0.693 AC: 46679 AN: 67346

Other (OTH) AF: 0.677 AC: 1418 AN: 2094

Alfa AF: 0.580 Hom.: 1626

Bravo AF: 0.682

Asia WGS AF: 0.633 AC: 2205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.16
PhyloP100		-4.0
BranchPoint Hunter		0.0
PromoterAI		-0.053	Neutral
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: rs896953; hg19: chr8-144660189; COSMIC: COSV52787017; COSMIC: COSV52787017;