rs6537860

chr1-115313723-A-Gchr1-115313723-A-T

Variant summary

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

The NM_002506.3(NGF):c.-136-19973T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,046 control chromosomes in the GnomAD database, including 28,599 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 0.59 (28599 hom., cov: 33)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NGF	NM_002506.3	c.-136-19973T>C		intron_variant		ENST00000369512.3
NGF-AS1	NR_157569.1	n.207+30483A>G		intron_variant, non_coding_transcript_variant
NGF	XM_006710663.4	c.-13+24481T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NGF	ENST00000369512.3	c.-136-19973T>C		intron_variant		1	NM_002506.3	P1
NGF-AS1	ENST00000425449.1	n.207+30483A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90133 AN: 151928 Hom.: 28596 Cov.: 33

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.689

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.593 AC: 90171 AN: 152046 Hom.: 28599 Cov.: 33 AF XY: 0.588 AC XY: 43714 AN XY: 74320

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.608

Alfa AF: 0.691 Hom.: 74225

Bravo AF: 0.575

Asia WGS AF: 0.362 AC: 1260 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	13
Dann	Benign	0.77

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: rs6537860; hg19: chr1-115856344;