1-115289162-C-T

Variant names:

• chr1-115289162-C-T
• rs2268793
• NM_002506.3:c.-12-2355G>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.-12-2355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0772 in 152,174 control chromosomes in the GnomAD database, including 664 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 0.077 (664 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 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.-12-2355G>A		intron	N/A	NP_002497.2
	NGF	NM_001437545.1		c.-12-2355G>A		intron	N/A	NP_001424474.1
	NGF-AS1	NR_157569.1		n.207+5922C>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.-12-2355G>A		intron	N/A	ENSP00000358525.2
	NGF	ENST00000675637.2		c.-12-2355G>A		intron	N/A	ENSP00000502831.1
	NGF	ENST00000676038.2		c.-12-2355G>A		intron	N/A	ENSP00000502380.1

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11732 AN: 152056 Hom.: 659 Cov.: 32

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0758

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0645

Gnomad OTH AF: 0.0821

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

GnomAD4 genome AF: 0.0772 AC: 11754 AN: 152174 Hom.: 664 Cov.: 32 AF XY: 0.0807 AC XY: 6004 AN XY: 74392

African (AFR) AF: 0.0369 AC: 1534 AN: 41540

American (AMR) AF: 0.133 AC: 2033 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 343 AN: 3472

East Asian (EAS) AF: 0.262 AC: 1350 AN: 5162

South Asian (SAS) AF: 0.212 AC: 1018 AN: 4810

European-Finnish (FIN) AF: 0.0758 AC: 802 AN: 10574

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0646 AC: 4391 AN: 68010

Other (OTH) AF: 0.0874 AC: 185 AN: 2116

Alfa AF: 0.0657 Hom.: 340

Bravo AF: 0.0793

Asia WGS AF: 0.246 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.70
PhyloP100		-0.13
PromoterAI		-0.0037	Neutral
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: rs2268793; hg19: chr1-115831783;