rs17033692

Variant names:

• chr1-115327229-T-C
• rs17033692
• NM_002506.3:c.-137+10975A>G

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+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
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 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.-137+10975A>G		intron	N/A	NP_002497.2
	NGF	NM_001437545.1		c.-13+10975A>G		intron	N/A	NP_001424474.1
	NGF-AS1	NR_157569.1		n.208-38441T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	ENST00000369512.3	TSL:1 MANE Select	c.-137+10975A>G		intron	N/A	ENSP00000358525.2
	NGF	ENST00000675637.2		c.-13+10975A>G		intron	N/A	ENSP00000502831.1
	NGF	ENST00000676038.2		c.-224+10975A>G		intron	N/A	ENSP00000502380.1

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

African (AFR) AF: 0.0846 AC: 3517 AN: 41570

American (AMR) AF: 0.151 AC: 2308 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0991 AC: 344 AN: 3470

East Asian (EAS) AF: 0.254 AC: 1319 AN: 5184

South Asian (SAS) AF: 0.124 AC: 598 AN: 4824

European-Finnish (FIN) AF: 0.107 AC: 1135 AN: 10598

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0692 AC: 4706 AN: 68028

Other (OTH) AF: 0.0943 AC: 199 AN: 2110

Alfa AF: 0.0788 Hom.: 2313

Bravo AF: 0.0989

Asia WGS AF: 0.181 AC: 627 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.6
DANN	Benign	0.36
PhyloP100		-0.32
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: rs17033692; hg19: chr1-115869850;