rs4565713

Positions:

• chr1-115326878-G-A
• chr1-115326878-G-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+11326C>T		intron_variant		ENST00000369512.3	NP_002497.2
NGF	XM_006710663.4	c.-13+11326C>T		intron_variant			XP_006710726.1
NGF-AS1	NR_157569.1	n.208-38792G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+11326C>T		intron_variant		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

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.589

Alfa AF: 0.666 Hom.: 44796

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4565713; hg19: chr1-115869499;