chr1-115287322-C-A

Position:

• chr1-115287322-C-A

Variant summary

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

The NM_002506.3(NGF):​c.-12-515G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,000 control chromosomes in the GnomAD database, including 9,080 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 0.34 (9080 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGF	NM_002506.3	c.-12-515G>T		intron_variant		ENST00000369512.3	NP_002497.2
NGF	XM_011541518.3	c.154-515G>T		intron_variant			XP_011539820.1
NGF	XM_006710663.4	c.-12-515G>T		intron_variant			XP_006710726.1
NGF-AS1	NR_157569.1	n.207+4082C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-12-515G>T		intron_variant		1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51914 AN: 151882 Hom.: 9076 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.342 AC: 51922 AN: 152000 Hom.: 9080 Cov.: 32 AF XY: 0.348 AC XY: 25874 AN XY: 74298

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.358

Alfa AF: 0.251 Hom.: 869

Bravo AF: 0.345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.42
DANN	Benign	0.56

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: rs6328; hg19: chr1-115829943;