NM_002506.3:c.-12-558G>A

Variant names:

• chr1-115287365-C-T
• rs6327
• NM_002506.3:c.-12-558G>A

Variant summary

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

The NM_002506.3(NGF):​c.-12-558G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,934 control chromosomes in the GnomAD database, including 10,862 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 0.35 (10862 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33
• Publications: 8 publications found

Genes affected

NGF (HGNC:7808): (nerve growth factor) This gene is a member of the NGF-beta family and encodes a secreted protein which homodimerizes and is incorporated into a larger complex. This protein has nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy, type 5 (HSAN5), and dysregulation of this gene's expression is associated with allergic rhinitis. [provided by RefSeq, Jul 2008]

NGF-AS1 (HGNC:53922): (NGF antisense RNA 1)

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 (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-12-558G>A		intron_variant	Intron 2 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-12-558G>A		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.207+4125C>T		intron_variant	Intron 1 of 1
NGF	XM_011541518.3	c.154-558G>A		intron_variant	Intron 2 of 2		XP_011539820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-12-558G>A		intron_variant	Intron 2 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53913 AN: 151818 Hom.: 10855 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.355 AC: 53933 AN: 151934 Hom.: 10862 Cov.: 32 AF XY: 0.352 AC XY: 26117 AN XY: 74252

African (AFR) AF: 0.190 AC: 7884 AN: 41436

American (AMR) AF: 0.357 AC: 5455 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1369 AN: 3468

East Asian (EAS) AF: 0.164 AC: 845 AN: 5164

South Asian (SAS) AF: 0.221 AC: 1061 AN: 4804

European-Finnish (FIN) AF: 0.484 AC: 5103 AN: 10550

Middle Eastern (MID) AF: 0.290 AC: 84 AN: 290

European-Non Finnish (NFE) AF: 0.455 AC: 30904 AN: 67936

Other (OTH) AF: 0.377 AC: 794 AN: 2108

Alfa AF: 0.397 Hom.: 16364

Bravo AF: 0.340

Asia WGS AF: 0.182 AC: 634 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	0.052
DANN	Benign	0.75
PhyloP100		-3.3
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: rs6327; hg19: chr1-115829986;