chr1-115330426-G-T

Position:

• chr1-115330426-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002506.3(NGF):​c.-137+7778C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,096 control chromosomes in the GnomAD database, including 38,384 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 0.69 (38384 hom., cov: 33)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+7778C>A		intron_variant		ENST00000369512.3	NP_002497.2
NGF	XM_006710663.4	c.-13+7778C>A		intron_variant			XP_006710726.1
NGF-AS1	NR_157569.1	n.208-35244G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+7778C>A		intron_variant		1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104876 AN: 151980 Hom.: 38372 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.690 AC: 104926 AN: 152096 Hom.: 38384 Cov.: 33 AF XY: 0.694 AC XY: 51636 AN XY: 74366

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.839

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.696

Alfa AF: 0.775 Hom.: 60291

Bravo AF: 0.671

Asia WGS AF: 0.661 AC: 2302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.22
DANN	Benign	0.42

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: rs10776799; hg19: chr1-115873047;