rs4652795

chr1-183297047-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMNAT2	NM_015039.4	c.86-3254G>A		intron_variant		ENST00000287713.7
NMNAT2	NM_170706.4	c.71-3254G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NMNAT2	ENST00000287713.7	c.86-3254G>A		intron_variant		1	NM_015039.4	P1
NMNAT2	ENST00000294868.8	c.71-3254G>A		intron_variant		1

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

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.576

Alfa AF: 0.620 Hom.: 59633

Bravo AF: 0.533

Asia WGS AF: 0.496 AC: 1725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.67
Dann	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs4652795; hg19: chr1-183266182;