chr1-183297047-C-T

Variant names:

• chr1-183297047-C-T
• rs4652795
• NM_015039.4:c.86-3254G>A

Variant summary

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

The NM_015039.4(NMNAT2):​c.86-3254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 150,260 control chromosomes in the GnomAD database, including 24,094 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 0.55 (24094 hom., cov: 27)
• Consequence: NMNAT2 NM_015039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 10 publications found

Genes affected

NMNAT2 (HGNC:16789): (nicotinamide nucleotide adenylyltransferase 2) This gene product belongs to the nicotinamide mononucleotide adenylyltransferase (NMNAT) enzyme family, members of which catalyze an essential step in NAD (NADP) biosynthetic pathway. Unlike the other human family member, which is localized to the nucleus, and is ubiquitously expressed; this enzyme is cytoplasmic, and is predominantly expressed in the brain. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015039.4. 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
	NMNAT2	NM_015039.4	MANE Select	c.86-3254G>A		intron	N/A	NP_055854.1
	NMNAT2	NM_170706.4		c.71-3254G>A		intron	N/A	NP_733820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMNAT2	ENST00000287713.7	TSL:1 MANE Select	c.86-3254G>A		intron	N/A	ENSP00000287713.6
	NMNAT2	ENST00000294868.8	TSL:1	c.71-3254G>A		intron	N/A	ENSP00000294868.4

Frequencies

GnomAD3 genomes AF: 0.551 AC: 82678 AN: 150142 Hom.: 24074 Cov.: 27

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.576

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.551 AC: 82726 AN: 150260 Hom.: 24094 Cov.: 27 AF XY: 0.555 AC XY: 40593 AN XY: 73204

African (AFR) AF: 0.351 AC: 14295 AN: 40780

American (AMR) AF: 0.595 AC: 8889 AN: 14952

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2349 AN: 3462

East Asian (EAS) AF: 0.509 AC: 2592 AN: 5088

South Asian (SAS) AF: 0.510 AC: 2390 AN: 4686

European-Finnish (FIN) AF: 0.694 AC: 7139 AN: 10288

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.635 AC: 43034 AN: 67718

Other (OTH) AF: 0.576 AC: 1201 AN: 2086

Alfa AF: 0.605 Hom.: 123842

Bravo AF: 0.533

Asia WGS AF: 0.496 AC: 1725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.67
DANN	Benign	0.40
PhyloP100		-1.6
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: rs4652795; hg19: chr1-183266182;