rs6673867

Variant names:

• chr1-115335621-T-G
• rs6673867
• NM_002506.3:c.-137+2583A>C

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+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
• Publications: 4 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=-0.89).
• 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 rank	MANE	Protein	UniProt
NGF	NM_002506.3	c.-137+2583A>C		intron_variant	Intron 1 of 2	ENST00000369512.3	NP_002497.2
NGF	NM_001437545.1	c.-13+2583A>C		intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1	n.208-30049T>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3	c.-137+2583A>C		intron_variant	Intron 1 of 2	1	NM_002506.3	ENSP00000358525.2

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

African (AFR) AF: 0.903 AC: 37551 AN: 41566

American (AMR) AF: 0.712 AC: 10892 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2349 AN: 3472

East Asian (EAS) AF: 0.881 AC: 4530 AN: 5142

South Asian (SAS) AF: 0.665 AC: 3204 AN: 4816

European-Finnish (FIN) AF: 0.468 AC: 4956 AN: 10592

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34108 AN: 67982

Other (OTH) AF: 0.656 AC: 1388 AN: 2116

Alfa AF: 0.535 Hom.: 11904

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
PhyloP100		-0.20
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: rs6673867; hg19: chr1-115878242; COSMIC: COSV65687314;