rs6686615

Variant names:

• chr1-115302425-G-A
• rs6686615
• NM_002506.3:c.-136-8675C>T

Variant summary

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

The NM_002506.3(NGF):​c.-136-8675C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,966 control chromosomes in the GnomAD database, including 11,146 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 0.37 (11146 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 4 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002506.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	NM_002506.3	MANE Select	c.-136-8675C>T		intron	N/A	NP_002497.2
	NGF	NM_001437545.1		c.-12-15618C>T		intron	N/A	NP_001424474.1
	NGF-AS1	NR_157569.1		n.207+19185G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	ENST00000369512.3	TSL:1 MANE Select	c.-136-8675C>T		intron	N/A	ENSP00000358525.2
	NGF	ENST00000675637.2		c.-12-15618C>T		intron	N/A	ENSP00000502831.1
	NGF	ENST00000676038.2		c.-223-1942C>T		intron	N/A	ENSP00000502380.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55938 AN: 151848 Hom.: 11148 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.368 AC: 55940 AN: 151966 Hom.: 11146 Cov.: 32 AF XY: 0.366 AC XY: 27177 AN XY: 74276

African (AFR) AF: 0.251 AC: 10386 AN: 41454

American (AMR) AF: 0.306 AC: 4677 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3468

East Asian (EAS) AF: 0.128 AC: 665 AN: 5178

South Asian (SAS) AF: 0.323 AC: 1552 AN: 4810

European-Finnish (FIN) AF: 0.489 AC: 5155 AN: 10550

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30847 AN: 67930

Other (OTH) AF: 0.388 AC: 818 AN: 2110

Alfa AF: 0.426 Hom.: 24090

Bravo AF: 0.351

Asia WGS AF: 0.210 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.7
DANN	Benign	0.58
PhyloP100		0.34
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: rs6686615; hg19: chr1-115845046;