1-183271560-C-G

Position:

• chr1-183271560-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015039.4(NMNAT2):​c.651+6993G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 152,232 control chromosomes in the GnomAD database, including 143 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 0.039 (143 hom., cov: 32)
• Consequence: NMNAT2 NM_015039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMNAT2	NM_015039.4	c.651+6993G>C		intron_variant		ENST00000287713.7	NP_055854.1
NMNAT2	NM_170706.4	c.636+6993G>C		intron_variant			NP_733820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMNAT2	ENST00000287713.7	c.651+6993G>C		intron_variant		1	NM_015039.4	ENSP00000287713	P1
NMNAT2	ENST00000294868.8	c.636+6993G>C		intron_variant		1		ENSP00000294868
NMNAT2	ENST00000464047.1	n.133+6993G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0391 AC: 5950 AN: 152114 Hom.: 142 Cov.: 32

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0540

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0257

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0356

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0391 AC: 5958 AN: 152232 Hom.: 143 Cov.: 32 AF XY: 0.0401 AC XY: 2982 AN XY: 74426

Gnomad4 AFR AF: 0.0285

Gnomad4 AMR AF: 0.0540

Gnomad4 ASJ AF: 0.0481

Gnomad4 EAS AF: 0.0773

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0257

Gnomad4 NFE AF: 0.0356

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0339 Hom.: 12

Bravo AF: 0.0413

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.57

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: rs16860717; hg19: chr1-183240695;