1-115314630-G-A

Position:

• chr1-115314630-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• 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/exons	MANE	Protein	UniProt
NGF	NM_002506.3	c.-136-20880C>T		intron_variant		ENST00000369512.3	NP_002497.2
NGF-AS1	NR_157569.1	n.207+31390G>A		intron_variant, non_coding_transcript_variant
NGF	XM_006710663.4	c.-13+23574C>T		intron_variant			XP_006710726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-136-20880C>T		intron_variant		1	NM_002506.3	ENSP00000358525	P1
NGF-AS1	ENST00000425449.1	n.207+31390G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.548

Alfa AF: 0.608 Hom.: 57801

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

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: rs12145726; hg19: chr1-115857251;