1-183389270-C-T

Variant names:

• chr1-183389270-C-T
• rs2078087
• NM_015039.4:c.85+28913G>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.85+28913G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,168 control chromosomes in the GnomAD database, including 2,065 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 (2065 hom., cov: 32)
• Consequence: NMNAT2 NM_015039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702
• Publications: 13 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]

ENSG00000305685 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NMNAT2	NM_015039.4	c.85+28913G>A		intron_variant	Intron 1 of 10	ENST00000287713.7	NP_055854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NMNAT2	ENST00000287713.7	c.85+28913G>A		intron_variant	Intron 1 of 10	1	NM_015039.4	ENSP00000287713.6
ENSG00000305685	ENST00000812392.1	n.*92G>A		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23826 AN: 152050 Hom.: 2052 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.0974

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.157 AC: 23875 AN: 152168 Hom.: 2065 Cov.: 32 AF XY: 0.158 AC XY: 11782 AN XY: 74408

African (AFR) AF: 0.228 AC: 9471 AN: 41480

American (AMR) AF: 0.148 AC: 2266 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1231 AN: 5174

South Asian (SAS) AF: 0.247 AC: 1187 AN: 4814

European-Finnish (FIN) AF: 0.0974 AC: 1033 AN: 10602

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7822 AN: 68016

Other (OTH) AF: 0.140 AC: 296 AN: 2112

Alfa AF: 0.128 Hom.: 5469

Bravo AF: 0.162

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.55
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2078087; hg19: chr1-183358405;