rs4565713

Variant names:

• chr1-115326878-G-A
• rs4565713
• NM_002506.3:c.-137+11326C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-115326878-G-A
• chr1-115326878-G-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.-137+11326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,996 control chromosomes in the GnomAD database, including 27,761 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 (27761 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+11326C>T		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-13+11326C>T		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.208-38792G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+11326C>T		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89512 AN: 151878 Hom.: 27748 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.589 AC: 89554 AN: 151996 Hom.: 27761 Cov.: 32 AF XY: 0.590 AC XY: 43826 AN XY: 74302

African (AFR) AF: 0.419 AC: 17344 AN: 41410

American (AMR) AF: 0.576 AC: 8799 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2003 AN: 3472

East Asian (EAS) AF: 0.344 AC: 1774 AN: 5162

South Asian (SAS) AF: 0.573 AC: 2756 AN: 4808

European-Finnish (FIN) AF: 0.718 AC: 7596 AN: 10574

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47305 AN: 67964

Other (OTH) AF: 0.589 AC: 1246 AN: 2116

Alfa AF: 0.657 Hom.: 55707

Bravo AF: 0.569

Asia WGS AF: 0.456 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
DANN	Benign	0.21
PhyloP100		-0.38
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: rs4565713; hg19: chr1-115869499;