rs17033692

Positions:

• chr1-115327229-T-C

Variant summary

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

The NM_002506.3(NGF):​c.-137+10975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0934 in 152,288 control chromosomes in the GnomAD database, including 802 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 0.093 (802 hom., cov: 33)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+10975A>G		intron_variant		ENST00000369512.3	NP_002497.2
NGF	XM_006710663.4	c.-13+10975A>G		intron_variant			XP_006710726.1
NGF-AS1	NR_157569.1	n.208-38441T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+10975A>G		intron_variant		1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.0934 AC: 14206 AN: 152170 Hom.: 794 Cov.: 33

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.0929

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

GnomAD4 genome AF: 0.0934 AC: 14227 AN: 152288 Hom.: 802 Cov.: 33 AF XY: 0.0976 AC XY: 7267 AN XY: 74454

Gnomad4 AFR AF: 0.0846

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0991

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0692

Gnomad4 OTH AF: 0.0943

Alfa AF: 0.0763 Hom.: 995

Bravo AF: 0.0989

Asia WGS AF: 0.181 AC: 627 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.36

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: rs17033692; hg19: chr1-115869850;