chr1-115297050-T-C

Variant names:

• chr1-115297050-T-C
• rs6678788
• NM_002506.3:c.-136-3300A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002506.3(NGF):​c.-136-3300A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,128 control chromosomes in the GnomAD database, including 35,240 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 0.68 (35240 hom., cov: 33)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002506.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	NM_002506.3	MANE Select	c.-136-3300A>G		intron	N/A	NP_002497.2	P01138
	NGF	NM_001437545.1		c.-12-10243A>G		intron	N/A	NP_001424474.1
	NGF-AS1	NR_157569.1		n.207+13810T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	ENST00000369512.3	TSL:1 MANE Select	c.-136-3300A>G		intron	N/A	ENSP00000358525.2	P01138
	NGF	ENST00000675637.2		c.-12-10243A>G		intron	N/A	ENSP00000502831.1	P01138
	NGF	ENST00000676038.2		c.-136-3300A>G		intron	N/A	ENSP00000502380.1	P01138

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102991 AN: 152010 Hom.: 35225 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.677 AC: 103038 AN: 152128 Hom.: 35240 Cov.: 33 AF XY: 0.679 AC XY: 50514 AN XY: 74394

African (AFR) AF: 0.583 AC: 24169 AN: 41476

American (AMR) AF: 0.698 AC: 10674 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2250 AN: 3472

East Asian (EAS) AF: 0.581 AC: 2999 AN: 5162

South Asian (SAS) AF: 0.671 AC: 3236 AN: 4822

European-Finnish (FIN) AF: 0.767 AC: 8123 AN: 10590

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49315 AN: 67996

Other (OTH) AF: 0.662 AC: 1398 AN: 2112

Alfa AF: 0.708 Hom.: 18986

Bravo AF: 0.671

Asia WGS AF: 0.603 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.63
PhyloP100		-0.046
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: rs6678788; hg19: chr1-115839671; COSMIC: COSV65687190;