rs6328

Variant names:

• chr1-115287322-C-A
• rs6328
• NM_002506.3:c.-12-515G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-115287322-C-A
• chr1-115287322-C-G
• chr1-115287322-C-T

Variant summary

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

The NM_002506.3(NGF):​c.-12-515G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,000 control chromosomes in the GnomAD database, including 9,080 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 0.34 (9080 hom., cov: 32)
• Consequence: NGF NM_002506.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807
• Publications: 10 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 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.-12-515G>T		intron	N/A	NP_002497.2	P01138
	NGF	NM_001437545.1		c.-12-515G>T		intron	N/A	NP_001424474.1
	NGF-AS1	NR_157569.1		n.207+4082C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGF	ENST00000369512.3	TSL:1 MANE Select	c.-12-515G>T		intron	N/A	ENSP00000358525.2	P01138
	NGF	ENST00000680540.1		c.-527G>T		5_prime_UTR	Exon 1 of 1	ENSP00000506569.1	P01138
	NGF	ENST00000675637.2		c.-12-515G>T		intron	N/A	ENSP00000502831.1	P01138

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51914 AN: 151882 Hom.: 9076 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.342 AC: 51922 AN: 152000 Hom.: 9080 Cov.: 32 AF XY: 0.348 AC XY: 25874 AN XY: 74298

African (AFR) AF: 0.285 AC: 11828 AN: 41436

American (AMR) AF: 0.388 AC: 5925 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2763 AN: 5150

South Asian (SAS) AF: 0.490 AC: 2361 AN: 4822

European-Finnish (FIN) AF: 0.313 AC: 3306 AN: 10566

Middle Eastern (MID) AF: 0.414 AC: 120 AN: 290

European-Non Finnish (NFE) AF: 0.341 AC: 23151 AN: 67974

Other (OTH) AF: 0.358 AC: 756 AN: 2110

Alfa AF: 0.252 Hom.: 902

Bravo AF: 0.345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.42
DANN	Benign	0.56
PhyloP100		-0.81
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: rs6328; hg19: chr1-115829943;