chr1-115290960-T-C

Variant names:

• chr1-115290960-T-C
• rs2254527
• NM_002506.3:c.-13+2667A>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.-13+2667A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,168 control chromosomes in the GnomAD database, including 49,913 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 0.81 (49913 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 7 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 = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-13+2667A>G		intron_variant	Intron 2 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-12-4153A>G		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.207+7720T>C		intron_variant	Intron 1 of 1
NGF	XM_011541518.3	c.153+2667A>G		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+2667A>G		intron_variant	Intron 2 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122792 AN: 152050 Hom.: 49874 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.808 AC: 122883 AN: 152168 Hom.: 49913 Cov.: 32 AF XY: 0.807 AC XY: 60055 AN XY: 74384

African (AFR) AF: 0.891 AC: 37017 AN: 41554

American (AMR) AF: 0.786 AC: 12002 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2390 AN: 3470

East Asian (EAS) AF: 0.666 AC: 3441 AN: 5164

South Asian (SAS) AF: 0.718 AC: 3453 AN: 4812

European-Finnish (FIN) AF: 0.830 AC: 8792 AN: 10596

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53241 AN: 67982

Other (OTH) AF: 0.773 AC: 1629 AN: 2108

Alfa AF: 0.782 Hom.: 77701

Bravo AF: 0.810

Asia WGS AF: 0.691 AC: 2404 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	1.8
DANN	Benign	0.46
PhyloP100		-0.15
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: rs2254527; hg19: chr1-115833581;