rs10858074

Variant names:

• chr1-115327689-A-G
• rs10858074
• NM_002506.3:c.-137+10515T>C

Variant summary

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

The NM_002506.3(NGF):​c.-137+10515T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,270 control chromosomes in the GnomAD database, including 2,010 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 0.11 (2010 hom., cov: 33)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+10515T>C		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-13+10515T>C		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.208-37981A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+10515T>C		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17411 AN: 152152 Hom.: 1999 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.0512

Gnomad SAS AF: 0.0349

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.115 AC: 17458 AN: 152270 Hom.: 2010 Cov.: 33 AF XY: 0.110 AC XY: 8160 AN XY: 74478

African (AFR) AF: 0.298 AC: 12361 AN: 41516

American (AMR) AF: 0.0521 AC: 797 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3466

East Asian (EAS) AF: 0.0511 AC: 265 AN: 5186

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4832

European-Finnish (FIN) AF: 0.0148 AC: 157 AN: 10628

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0504 AC: 3430 AN: 68024

Other (OTH) AF: 0.0771 AC: 163 AN: 2114

Alfa AF: 0.0619 Hom.: 902

Bravo AF: 0.125

Asia WGS AF: 0.0410 AC: 141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.9
DANN	Benign	0.65
PhyloP100		1.7
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: rs10858074; hg19: chr1-115870310;