chr1-115308870-A-G

Variant names:

• chr1-115308870-A-G
• rs4529705
• NM_002506.3:c.-136-15120T>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.-136-15120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,988 control chromosomes in the GnomAD database, including 28,534 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 0.59 (28534 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-136-15120T>C		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-12-22063T>C		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.207+25630A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-136-15120T>C		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90011 AN: 151868 Hom.: 28532 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.592 AC: 90047 AN: 151988 Hom.: 28534 Cov.: 32 AF XY: 0.588 AC XY: 43650 AN XY: 74284

African (AFR) AF: 0.411 AC: 17042 AN: 41434

American (AMR) AF: 0.544 AC: 8304 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2149 AN: 3470

East Asian (EAS) AF: 0.255 AC: 1319 AN: 5166

South Asian (SAS) AF: 0.525 AC: 2530 AN: 4818

European-Finnish (FIN) AF: 0.684 AC: 7220 AN: 10548

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.726 AC: 49337 AN: 67972

Other (OTH) AF: 0.608 AC: 1280 AN: 2104

Alfa AF: 0.653 Hom.: 4209

Bravo AF: 0.573

Asia WGS AF: 0.363 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.78
PhyloP100		0.098
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: rs4529705; hg19: chr1-115851491; COSMIC: COSV65687275;