chr1-115313723-A-G

Variant names:

• chr1-115313723-A-G
• rs6537860
• NM_002506.3:c.-136-19973T>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.-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
• Publications: 15 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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.721 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.-136-19973T>C		intron	N/A	NP_002497.2
	NGF	NM_001437545.1		c.-13+24481T>C		intron	N/A	NP_001424474.1
	NGF-AS1	NR_157569.1		n.207+30483A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	ENST00000369512.3	TSL:1 MANE Select	c.-136-19973T>C		intron	N/A	ENSP00000358525.2
	NGF	ENST00000675637.2		c.-13+24481T>C		intron	N/A	ENSP00000502831.1
	NGF	ENST00000676038.2		c.-223-13240T>C		intron	N/A	ENSP00000502380.1

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

African (AFR) AF: 0.411 AC: 17053 AN: 41468

American (AMR) AF: 0.547 AC: 8352 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2153 AN: 3472

East Asian (EAS) AF: 0.257 AC: 1327 AN: 5172

South Asian (SAS) AF: 0.526 AC: 2531 AN: 4816

European-Finnish (FIN) AF: 0.685 AC: 7231 AN: 10560

Middle Eastern (MID) AF: 0.686 AC: 199 AN: 290

European-Non Finnish (NFE) AF: 0.726 AC: 49381 AN: 67980

Other (OTH) AF: 0.608 AC: 1282 AN: 2108

Alfa AF: 0.671 Hom.: 111263

Bravo AF: 0.575

Asia WGS AF: 0.362 AC: 1260 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		2.1
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: rs6537860; hg19: chr1-115856344;