chr1-115335621-T-G

Position:

• chr1-115335621-T-G

Variant summary

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

The NM_002506.3(NGF):​c.-137+2583A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,188 control chromosomes in the GnomAD database, including 35,194 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 0.65 (35194 hom., cov: 34)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+2583A>C		intron_variant		ENST00000369512.3	NP_002497.2
NGF-AS1	NR_157569.1	n.208-30049T>G		intron_variant, non_coding_transcript_variant
NGF	XM_006710663.4	c.-13+2583A>C		intron_variant			XP_006710726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+2583A>C		intron_variant		1	NM_002506.3	ENSP00000358525	P1
NGF-AS1	ENST00000425449.1	n.208-30049T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99520 AN: 152072 Hom.: 35130 Cov.: 34

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.655 AC: 99644 AN: 152188 Hom.: 35194 Cov.: 34 AF XY: 0.655 AC XY: 48694 AN XY: 74390

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.881

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.656

Alfa AF: 0.533 Hom.: 9933

Bravo AF: 0.685

Asia WGS AF: 0.789 AC: 2737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.80

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: rs6673867; hg19: chr1-115878242; COSMIC: COSV65687314;