rs4626883

Variant names:

• chr1-115307317-G-A
• rs4626883
• NM_002506.3:c.-136-13567C>T

Variant summary

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

The NM_002506.3(NGF):​c.-136-13567C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 152,230 control chromosomes in the GnomAD database, including 312 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 0.052 (312 hom., cov: 33)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0822 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	NM_002506.3	MANE Select	c.-136-13567C>T		intron	N/A	NP_002497.2	P01138
	NGF	NM_001437545.1		c.-12-20510C>T		intron	N/A	NP_001424474.1
	NGF-AS1	NR_157569.1		n.207+24077G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	ENST00000369512.3	TSL:1 MANE Select	c.-136-13567C>T		intron	N/A	ENSP00000358525.2	P01138
	NGF	ENST00000675637.2		c.-12-20510C>T		intron	N/A	ENSP00000502831.1	P01138
	NGF	ENST00000676038.2		c.-223-6834C>T		intron	N/A	ENSP00000502380.1	P01138

Frequencies

GnomAD3 genomes AF: 0.0523 AC: 7953 AN: 152112 Hom.: 312 Cov.: 33

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0692

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.0358

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

GnomAD4 genome AF: 0.0522 AC: 7949 AN: 152230 Hom.: 312 Cov.: 33 AF XY: 0.0506 AC XY: 3769 AN XY: 74430

African (AFR) AF: 0.0133 AC: 552 AN: 41542

American (AMR) AF: 0.0322 AC: 493 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0320 AC: 154 AN: 4818

European-Finnish (FIN) AF: 0.0692 AC: 734 AN: 10600

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0840 AC: 5710 AN: 67994

Other (OTH) AF: 0.0354 AC: 75 AN: 2116

Alfa AF: 0.0739 Hom.: 230

Bravo AF: 0.0488

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.43
PhyloP100		0.025
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: rs4626883; hg19: chr1-115849938;