Genetic Variant NGF:c.-13+145C>A (chr1-115293482-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The NM_002506.3(NGF):c.-13+145C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 152,558 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 114 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 0 hom. )

Consequence

NGF
NM_002506.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.329

Publications

1 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=-0.91).

BP6

Variant 1-115293482-G-T is Benign according to our data. Variant chr1-115293482-G-T is described in ClinVar as Benign. ClinVar VariationId is 1296050.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NGF	NM_002506.3 link	c.-13+145C>A	intron_variant	Intron 2 of 2	ENST00000369512.3	NP_002497.2	P01138
NGF	NM_001437545.1 link	c.-12-6675C>A	intron_variant	Intron 1 of 1		NP_001424474.1
NGF-AS1	NR_157569.1 link	n.207+10242G>T	intron_variant	Intron 1 of 1
NGF	XM_011541518.3 link	c.153+145C>A	intron_variant	Intron 2 of 2		XP_011539820.1	A0A346FYQ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGF	ENST00000369512.3 link	c.-13+145C>A		intron_variant	Intron 2 of 2	1	NM_002506.3	ENSP00000358525.2		P01138

Frequencies

GnomAD3 genomes

AF:

0.0228

AC:

3472

AN:

152196

Hom.:

114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0565

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0330

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.0818

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0196

GnomAD4 exome

AF:

0.00410

AC:

AN:

244

Hom.:

AF XY:

0.00

AC XY:

AN XY:

164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00562

AC:

AN:

178

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0228

AC:

3474

AN:

152314

Hom.:

114

Cov.:

AF XY:

0.0236

AC XY:

1755

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0564

AC:

2343

AN:

41574

American (AMR)

AF:

0.0331

AC:

507

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.0812

AC:

420

AN:

5170

South Asian (SAS)

AF:

0.0209

AC:

101

AN:

4824

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000500

AC:

AN:

68036

Other (OTH)

AF:

0.0203

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

164

328

491

655

819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0265

Hom.:

Bravo

AF:

0.0271

Asia WGS

AF:

0.0550

AC:

191

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 15, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.48

(source)

DANN

Benign

0.40

PhyloP100

-0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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