dbSNP rs11102930: NGF:c.-206C>T (chr1-115338434-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000680752.1(NGF):c.-206C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,962 control chromosomes in the GnomAD database, including 23,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.54 ( 23903 hom., cov: 32)

Consequence

NGF
ENST00000680752.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.277

Publications

13 publications found

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 links:

NGF-AS1 (HGNC:53922): (NGF antisense RNA 1)

NGF-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-115338434-G-A is Benign according to our data. Variant chr1-115338434-G-A is described in ClinVar as Benign. ClinVar VariationId is 667672.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NGF-AS1	NR_157569.1 link	n.208-27236G>A	intron_variant	Intron 1 of 1
NGF	NM_002506.3 link	c.-367C>T	upstream_gene_variant		ENST00000369512.3	NP_002497.2	P01138
NGF	NM_001437545.1 link	c.-243C>T	upstream_gene_variant			NP_001424474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3 link	c.-367C>T		upstream_gene_variant		1	NM_002506.3	ENSP00000358525.2		P01138

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82755

AN:

151842

Hom.:

23887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.704

Gnomad AMR

AF:

0.521

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.513

Gnomad FIN

AF:

0.709

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.649

Gnomad OTH

AF:

0.547

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

GnomAD4 genome

AF:

0.545

AC:

82801

AN:

151962

Hom.:

23903

Cov.:

AF XY:

0.546

AC XY:

40532

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.355

AC:

14729

AN:

41458

American (AMR)

AF:

0.521

AC:

7965

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1945

AN:

3466

East Asian (EAS)

AF:

0.427

AC:

2189

AN:

5122

South Asian (SAS)

AF:

0.513

AC:

2465

AN:

4808

European-Finnish (FIN)

AF:

0.709

AC:

7504

AN:

10588

Middle Eastern (MID)

AF:

0.510

AC:

149

AN:

292

European-Non Finnish (NFE)

AF:

0.649

AC:

44062

AN:

67922

Other (OTH)

AF:

0.544

AC:

1151

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1790

3579

5369

7158

8948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.613

Hom.:

46105

Bravo

AF:

0.522

Asia WGS

AF:

0.469

AC:

1633

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 20, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.5

(source)

DANN

Benign

0.49

PhyloP100

0.28

PromoterAI

-0.023

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over