rs12145726

Variant names:

• chr1-115314630-G-A
• rs12145726
• NM_002506.3:c.-136-20880C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002506.3(NGF):​c.-136-20880C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,952 control chromosomes in the GnomAD database, including 21,645 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 0.51 (21645 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-136-20880C>T		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-13+23574C>T		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.207+31390G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-136-20880C>T		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77040 AN: 151832 Hom.: 21644 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.507 AC: 77064 AN: 151952 Hom.: 21645 Cov.: 32 AF XY: 0.505 AC XY: 37527 AN XY: 74258

African (AFR) AF: 0.288 AC: 11923 AN: 41418

American (AMR) AF: 0.499 AC: 7616 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1996 AN: 3472

East Asian (EAS) AF: 0.255 AC: 1315 AN: 5152

South Asian (SAS) AF: 0.477 AC: 2296 AN: 4818

European-Finnish (FIN) AF: 0.617 AC: 6506 AN: 10548

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43484 AN: 67968

Other (OTH) AF: 0.548 AC: 1157 AN: 2110

Alfa AF: 0.590 Hom.: 116582

Bravo AF: 0.489

Asia WGS AF: 0.335 AC: 1167 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	5.6
DANN	Benign	0.68
PhyloP100		0.34
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: rs12145726; hg19: chr1-115857251;