chr1-115337511-G-A

Variant names:

• chr1-115337511-G-A
• rs17540656
• NM_002506.3:c.-137+693C>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.-137+693C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,632 control chromosomes in the GnomAD database, including 15,683 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 0.42 (15683 hom., cov: 30)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 8 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+693C>T		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-13+693C>T		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.208-28159G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+693C>T		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63986 AN: 151522 Hom.: 15686 Cov.: 30

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.422 AC: 63968 AN: 151632 Hom.: 15683 Cov.: 30 AF XY: 0.420 AC XY: 31137 AN XY: 74074

African (AFR) AF: 0.215 AC: 8905 AN: 41360

American (AMR) AF: 0.340 AC: 5193 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1304 AN: 3458

East Asian (EAS) AF: 0.112 AC: 572 AN: 5114

South Asian (SAS) AF: 0.347 AC: 1666 AN: 4806

European-Finnish (FIN) AF: 0.621 AC: 6520 AN: 10502

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.565 AC: 38323 AN: 67792

Other (OTH) AF: 0.391 AC: 826 AN: 2110

Alfa AF: 0.495 Hom.: 35684

Bravo AF: 0.388

Asia WGS AF: 0.205 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.9
DANN	Benign	0.87
PhyloP100		-0.25
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: rs17540656; hg19: chr1-115880132; COSMIC: COSV65689077;