rs17540656

Positions:

• chr1-115337511-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369512.3(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 ENST00000369512.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+693C>T		intron_variant		ENST00000369512.3	NP_002497.2
NGF-AS1	NR_157569.1	n.208-28159G>A		intron_variant, non_coding_transcript_variant
NGF	XM_006710663.4	c.-13+693C>T		intron_variant			XP_006710726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+693C>T		intron_variant		1	NM_002506.3	ENSP00000358525	P1
NGF-AS1	ENST00000425449.1	n.208-28159G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.391

Alfa AF: 0.513 Hom.: 27243

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs17540656; hg19: chr1-115880132; COSMIC: COSV65689077;