1-115295088-A-G

Variant names:

• chr1-115295088-A-G
• rs2239622
• NM_002506.3:c.-136-1338T>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.-136-1338T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,094 control chromosomes in the GnomAD database, including 43,757 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 0.76 (43757 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 19 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-136-1338T>C		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-12-8281T>C		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.207+11848A>G		intron_variant	Intron 1 of 1
NGF	XM_011541518.3	c.30-1338T>C		intron_variant	Intron 1 of 2		XP_011539820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-136-1338T>C		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114997 AN: 151976 Hom.: 43724 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.731

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

GnomAD4 genome AF: 0.757 AC: 115076 AN: 152094 Hom.: 43757 Cov.: 32 AF XY: 0.757 AC XY: 56310 AN XY: 74344

African (AFR) AF: 0.809 AC: 33573 AN: 41490

American (AMR) AF: 0.759 AC: 11608 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2229 AN: 3472

East Asian (EAS) AF: 0.596 AC: 3068 AN: 5150

South Asian (SAS) AF: 0.661 AC: 3185 AN: 4816

European-Finnish (FIN) AF: 0.812 AC: 8575 AN: 10564

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50451 AN: 67996

Other (OTH) AF: 0.726 AC: 1531 AN: 2110

Alfa AF: 0.737 Hom.: 184785

Bravo AF: 0.756

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.67
DANN	Benign	0.49
PhyloP100		-0.30
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: rs2239622; hg19: chr1-115837709;