1-115303600-C-T

Variant names:

• chr1-115303600-C-T
• rs12058927
• NM_002506.3:c.-136-9850G>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.-136-9850G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,926 control chromosomes in the GnomAD database, including 5,484 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 0.25 (5484 hom., cov: 31)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-136-9850G>A		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-12-16793G>A		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.207+20360C>T		intron_variant	Intron 1 of 1
NGF	XM_011541518.3	c.-3175G>A		upstream_gene_variant			XP_011539820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-136-9850G>A		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37439 AN: 151806 Hom.: 5463 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.247 AC: 37504 AN: 151926 Hom.: 5484 Cov.: 31 AF XY: 0.244 AC XY: 18157 AN XY: 74264

African (AFR) AF: 0.411 AC: 17002 AN: 41386

American (AMR) AF: 0.244 AC: 3729 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 623 AN: 3468

East Asian (EAS) AF: 0.238 AC: 1224 AN: 5152

South Asian (SAS) AF: 0.180 AC: 867 AN: 4812

European-Finnish (FIN) AF: 0.130 AC: 1376 AN: 10570

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11923 AN: 67952

Other (OTH) AF: 0.225 AC: 475 AN: 2114

Alfa AF: 0.191 Hom.: 12259

Bravo AF: 0.261

Asia WGS AF: 0.210 AC: 728 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.34
DANN	Benign	0.55
PhyloP100		-0.90
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: rs12058927; hg19: chr1-115846221;