1-115292879-T-G

Variant names:

• chr1-115292879-T-G
• rs910330
• NM_002506.3:c.-13+748A>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.-13+748A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 151,732 control chromosomes in the GnomAD database, including 38,789 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 0.71 (38789 hom., cov: 28)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-13+748A>C		intron_variant	Intron 2 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-12-6072A>C		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.207+9639T>G		intron_variant	Intron 1 of 1
NGF	XM_011541518.3	c.153+748A>C		intron_variant	Intron 2 of 2		XP_011539820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-13+748A>C		intron_variant	Intron 2 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108252 AN: 151614 Hom.: 38769 Cov.: 28

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.714 AC: 108308 AN: 151732 Hom.: 38789 Cov.: 28 AF XY: 0.714 AC XY: 52929 AN XY: 74148

African (AFR) AF: 0.713 AC: 29496 AN: 41346

American (AMR) AF: 0.711 AC: 10837 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2250 AN: 3472

East Asian (EAS) AF: 0.580 AC: 2967 AN: 5118

South Asian (SAS) AF: 0.671 AC: 3209 AN: 4782

European-Finnish (FIN) AF: 0.770 AC: 8112 AN: 10534

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.723 AC: 49127 AN: 67928

Other (OTH) AF: 0.684 AC: 1440 AN: 2104

Alfa AF: 0.715 Hom.: 165439

Bravo AF: 0.711

Asia WGS AF: 0.607 AC: 2114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		0.42
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: rs910330; hg19: chr1-115835500;