NM_002506.3:c.-136-1548G>A

Variant names:

• chr1-115295298-C-T
• rs2856813
• NM_002506.3:c.-136-1548G>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.-136-1548G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,004 control chromosomes in the GnomAD database, including 16,778 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 0.44 (16778 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 13 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-136-1548G>A		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-12-8491G>A		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.207+12058C>T		intron_variant	Intron 1 of 1
NGF	XM_011541518.3	c.30-1548G>A		intron_variant	Intron 1 of 2		XP_011539820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-136-1548G>A		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67175 AN: 151886 Hom.: 16778 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.442 AC: 67187 AN: 152004 Hom.: 16778 Cov.: 32 AF XY: 0.445 AC XY: 33065 AN XY: 74284

African (AFR) AF: 0.204 AC: 8438 AN: 41454

American (AMR) AF: 0.469 AC: 7177 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1712 AN: 3468

East Asian (EAS) AF: 0.375 AC: 1936 AN: 5162

South Asian (SAS) AF: 0.553 AC: 2660 AN: 4810

European-Finnish (FIN) AF: 0.567 AC: 5982 AN: 10550

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37637 AN: 67958

Other (OTH) AF: 0.468 AC: 988 AN: 2112

Alfa AF: 0.517 Hom.: 35431

Bravo AF: 0.423

Asia WGS AF: 0.417 AC: 1451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.7
DANN	Benign	0.79
PhyloP100		-1.0
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: rs2856813; hg19: chr1-115837919; COSMIC: COSV65687185;