rs2239622

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002506.3(NGF):​c.-136-1338T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,094 control chromosomes in the GnomAD database, including 43,757 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 0.76 ( 43757 hom., cov: 32)

Consequence

NGF
NM_002506.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.300
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NGFNM_002506.3 linkuse as main transcriptc.-136-1338T>C intron_variant ENST00000369512.3
NGF-AS1NR_157569.1 linkuse as main transcriptn.207+11848A>G intron_variant, non_coding_transcript_variant
NGFXM_006710663.4 linkuse as main transcriptc.-12-8281T>C intron_variant
NGFXM_011541518.3 linkuse as main transcriptc.30-1338T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NGFENST00000369512.3 linkuse as main transcriptc.-136-1338T>C intron_variant 1 NM_002506.3 P1
NGF-AS1ENST00000425449.1 linkuse as main transcriptn.207+11848A>G intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.757
AC:
114997
AN:
151976
Hom.:
43724
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.809
Gnomad AMI
AF:
0.705
Gnomad AMR
AF:
0.759
Gnomad ASJ
AF:
0.642
Gnomad EAS
AF:
0.597
Gnomad SAS
AF:
0.663
Gnomad FIN
AF:
0.812
Gnomad MID
AF:
0.728
Gnomad NFE
AF:
0.742
Gnomad OTH
AF:
0.731
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.757
AC:
115076
AN:
152094
Hom.:
43757
Cov.:
32
AF XY:
0.757
AC XY:
56310
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.809
Gnomad4 AMR
AF:
0.759
Gnomad4 ASJ
AF:
0.642
Gnomad4 EAS
AF:
0.596
Gnomad4 SAS
AF:
0.661
Gnomad4 FIN
AF:
0.812
Gnomad4 NFE
AF:
0.742
Gnomad4 OTH
AF:
0.726
Alfa
AF:
0.732
Hom.:
84201
Bravo
AF:
0.756
Asia WGS
AF:
0.608
AC:
2116
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
0.67
DANN
Benign
0.49

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2239622; hg19: chr1-115837709; API