1-115304674-T-G

Variant names:

• chr1-115304674-T-G
• rs10776797
• NM_002506.3:c.-136-10924A>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.-136-10924A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 151,988 control chromosomes in the GnomAD database, including 51,762 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 0.82 (51762 hom., cov: 30)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-136-10924A>C		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-12-17867A>C		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.207+21434T>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-136-10924A>C		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125090 AN: 151870 Hom.: 51721 Cov.: 30

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.824 AC: 125186 AN: 151988 Hom.: 51762 Cov.: 30 AF XY: 0.823 AC XY: 61169 AN XY: 74286

African (AFR) AF: 0.884 AC: 36666 AN: 41470

American (AMR) AF: 0.810 AC: 12366 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2509 AN: 3472

East Asian (EAS) AF: 0.669 AC: 3424 AN: 5116

South Asian (SAS) AF: 0.744 AC: 3574 AN: 4802

European-Finnish (FIN) AF: 0.832 AC: 8798 AN: 10580

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55186 AN: 67962

Other (OTH) AF: 0.799 AC: 1691 AN: 2116

Alfa AF: 0.809 Hom.: 152017

Bravo AF: 0.827

Asia WGS AF: 0.705 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.75
PhyloP100		1.3
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: rs10776797; hg19: chr1-115847295;