rs2856811

Variant names:

• chr1-115295661-G-T
• rs2856811
• NM_002506.3:c.-136-1911C>A

Variant summary

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

The NM_002506.3(NGF):​c.-136-1911C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,958 control chromosomes in the GnomAD database, including 25,733 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 0.58 (25733 hom., cov: 31)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	NM_002506.3	MANE Select	c.-136-1911C>A		intron	N/A	NP_002497.2
	NGF	NM_001437545.1		c.-12-8854C>A		intron	N/A	NP_001424474.1
	NGF-AS1	NR_157569.1		n.207+12421G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	ENST00000369512.3	TSL:1 MANE Select	c.-136-1911C>A		intron	N/A	ENSP00000358525.2
	NGF	ENST00000675637.2		c.-12-8854C>A		intron	N/A	ENSP00000502831.1
	NGF	ENST00000676038.2		c.-136-1911C>A		intron	N/A	ENSP00000502380.1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87690 AN: 151838 Hom.: 25723 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.577 AC: 87725 AN: 151958 Hom.: 25733 Cov.: 31 AF XY: 0.575 AC XY: 42676 AN XY: 74270

African (AFR) AF: 0.504 AC: 20894 AN: 41420

American (AMR) AF: 0.534 AC: 8143 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1863 AN: 3472

East Asian (EAS) AF: 0.378 AC: 1949 AN: 5162

South Asian (SAS) AF: 0.588 AC: 2826 AN: 4810

European-Finnish (FIN) AF: 0.637 AC: 6729 AN: 10570

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43391 AN: 67958

Other (OTH) AF: 0.559 AC: 1178 AN: 2108

Alfa AF: 0.613 Hom.: 47499

Bravo AF: 0.566

Asia WGS AF: 0.446 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.23
DANN	Benign	0.63
PhyloP100		-0.70
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: rs2856811; hg19: chr1-115838282;