chr1-115319633-A-C

Variant names:

• chr1-115319633-A-C
• rs10776798
• NM_002506.3:c.-137+18571T>G

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+18571T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,212 control chromosomes in the GnomAD database, including 56,433 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 0.86 (56433 hom., cov: 31)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+18571T>G		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-13+18571T>G		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.207+36393A>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+18571T>G		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130404 AN: 152094 Hom.: 56377 Cov.: 31

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.857 AC: 130519 AN: 152212 Hom.: 56433 Cov.: 31 AF XY: 0.857 AC XY: 63749 AN XY: 74410

African (AFR) AF: 0.954 AC: 39657 AN: 41560

American (AMR) AF: 0.813 AC: 12425 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2417 AN: 3468

East Asian (EAS) AF: 0.652 AC: 3369 AN: 5166

South Asian (SAS) AF: 0.752 AC: 3621 AN: 4812

European-Finnish (FIN) AF: 0.879 AC: 9320 AN: 10602

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57051 AN: 68006

Other (OTH) AF: 0.801 AC: 1694 AN: 2114

Alfa AF: 0.832 Hom.: 226266

Bravo AF: 0.855

Asia WGS AF: 0.694 AC: 2418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		-1.1
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: rs10776798; hg19: chr1-115862254;