1-115286605-G-C

Variant names:

• chr1-115286605-G-C
• rs201087374
• NM_002506.3:c.191C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002506.3(NGF):​c.191C>G​(p.Ala64Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A64V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NGF NM_002506.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.68
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15858889).

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.191C>G	p.Ala64Gly	missense	Exon 3 of 3	NP_002497.2	P01138
	NGF	NM_001437545.1		c.191C>G	p.Ala64Gly	missense	Exon 2 of 2	NP_001424474.1
	NGF-AS1	NR_157569.1		n.207+3365G>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.191C>G	p.Ala64Gly	missense	Exon 3 of 3	ENSP00000358525.2	P01138
	NGF	ENST00000675637.2		c.191C>G	p.Ala64Gly	missense	Exon 2 of 2	ENSP00000502831.1	P01138
	NGF	ENST00000676038.2		c.191C>G	p.Ala64Gly	missense	Exon 4 of 4	ENSP00000502380.1	P01138

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461858 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.0072
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		3.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.082
Sift	Benign	0.11	T
Sift4G	Benign	0.34	T
Polyphen		0.0020	B
Vest4		0.089
MutPred		0.28		Loss of helix (P = 0.079)
MVP		0.50
MPC		0.45
ClinPred		0.44	T
GERP RS		5.1
Varity_R		0.14
gMVP		0.29
Mutation Taster		=86/14	polymorphism

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: rs201087374; hg19: chr1-115829226;