chr1-115318644-T-C

Variant names:

• chr1-115318644-T-C
• rs7523654
• NM_002506.3:c.-137+19560A>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.-137+19560A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,036 control chromosomes in the GnomAD database, including 25,917 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 0.55 (25917 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 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.-137+19560A>G		intron	N/A	NP_002497.2
	NGF	NM_001437545.1		c.-13+19560A>G		intron	N/A	NP_001424474.1
	NGF-AS1	NR_157569.1		n.207+35404T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	ENST00000369512.3	TSL:1 MANE Select	c.-137+19560A>G		intron	N/A	ENSP00000358525.2
	NGF	ENST00000675637.2		c.-13+19560A>G		intron	N/A	ENSP00000502831.1
	NGF	ENST00000676038.2		c.-223-18161A>G		intron	N/A	ENSP00000502380.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84285 AN: 151918 Hom.: 25908 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.555 AC: 84316 AN: 152036 Hom.: 25917 Cov.: 32 AF XY: 0.557 AC XY: 41380 AN XY: 74326

African (AFR) AF: 0.296 AC: 12260 AN: 41482

American (AMR) AF: 0.566 AC: 8643 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1974 AN: 3466

East Asian (EAS) AF: 0.348 AC: 1792 AN: 5150

South Asian (SAS) AF: 0.572 AC: 2754 AN: 4818

European-Finnish (FIN) AF: 0.717 AC: 7594 AN: 10586

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47370 AN: 67942

Other (OTH) AF: 0.569 AC: 1200 AN: 2108

Alfa AF: 0.598 Hom.: 11026

Bravo AF: 0.530

Asia WGS AF: 0.447 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.60
PhyloP100		0.60
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: rs7523654; hg19: chr1-115861265;