rs4332358

Variant names:

• chr1-115333024-C-T
• rs4332358
• NM_002506.3:c.-137+5180G>A

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+5180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,972 control chromosomes in the GnomAD database, including 13,574 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 0.39 (13574 hom., cov: 31)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• Publications: 13 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 (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+5180G>A		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-13+5180G>A		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.208-32646C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+5180G>A		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58906 AN: 151854 Hom.: 13549 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.388 AC: 58983 AN: 151972 Hom.: 13574 Cov.: 31 AF XY: 0.389 AC XY: 28909 AN XY: 74274

African (AFR) AF: 0.623 AC: 25777 AN: 41398

American (AMR) AF: 0.417 AC: 6372 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1439 AN: 3472

East Asian (EAS) AF: 0.550 AC: 2839 AN: 5164

South Asian (SAS) AF: 0.343 AC: 1651 AN: 4810

European-Finnish (FIN) AF: 0.257 AC: 2719 AN: 10584

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16940 AN: 67950

Other (OTH) AF: 0.396 AC: 835 AN: 2108

Alfa AF: 0.309 Hom.: 24973

Bravo AF: 0.413

Asia WGS AF: 0.426 AC: 1480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.43
DANN	Benign	0.50
PhyloP100		-0.83
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: rs4332358; hg19: chr1-115875645;