17-31219157-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000487476.5(NF1):c.*24T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 1,586,932 control chromosomes in the GnomAD database, including 355,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 25753 hom., cov: 30)

Exomes 𝑓: 0.67 ( 330153 hom. )

Consequence

NF1
ENST00000487476.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.554

Publications

25 publications found

Variant links:

Genes affected

NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]

NF1 Gene-Disease associations (from GenCC):

neurofibromatosis type 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
neurofibromatosis-Noonan syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
Moyamoya disease
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

NF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-31219157-T-C is Benign according to our data. Variant chr17-31219157-T-C is described in ClinVar as [Benign]. Clinvar id is 257278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3 link	c.1641+39T>C	intron_variant	Intron 14 of 57	ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.4 link	c.1641+39T>C	intron_variant	Intron 14 of 56		NP_000258.1	P21359-2
NF1	NM_001128147.3 link	c.1641+39T>C	intron_variant	Intron 14 of 14		NP_001121619.1	P21359-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9 link	c.1641+39T>C		intron_variant	Intron 14 of 57	1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81544

AN:

151730

Hom.:

25762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.722

Gnomad AMR

AF:

0.553

Gnomad ASJ

AF:

0.768

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.704

Gnomad OTH

AF:

0.605

GnomAD2 exomes

AF:

0.621

AC:

138781

AN:

223626

AF XY:

0.637

show subpopulations

Gnomad AFR exome

AF:

0.180

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.777

Gnomad EAS exome

AF:

0.564

Gnomad FIN exome

AF:

0.664

Gnomad NFE exome

AF:

0.700

Gnomad OTH exome

AF:

0.670

GnomAD4 exome

AF:

0.672

AC:

963725

AN:

1435084

Hom.:

330153

Cov.:

AF XY:

0.673

AC XY:

479547

AN XY:

712478

show subpopulations

African (AFR)

AF:

0.169

AC:

5559

AN:

32986

American (AMR)

AF:

0.512

AC:

21823

AN:

42662

Ashkenazi Jewish (ASJ)

AF:

0.775

AC:

19894

AN:

25660

East Asian (EAS)

AF:

0.556

AC:

21781

AN:

39190

South Asian (SAS)

AF:

0.634

AC:

53107

AN:

83822

European-Finnish (FIN)

AF:

0.657

AC:

34289

AN:

52184

Middle Eastern (MID)

AF:

0.758

AC:

4353

AN:

5740

European-Non Finnish (NFE)

AF:

0.698

AC:

763746

AN:

1093498

Other (OTH)

AF:

0.660

AC:

39173

AN:

59342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

15136

30273

45409

60546

75682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19214

38428

57642

76856

96070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.537

AC:

81528

AN:

151848

Hom.:

25753

Cov.:

AF XY:

0.534

AC XY:

39625

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.186

AC:

7717

AN:

41406

American (AMR)

AF:

0.553

AC:

8442

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.768

AC:

2662

AN:

3466

East Asian (EAS)

AF:

0.559

AC:

2873

AN:

5144

South Asian (SAS)

AF:

0.619

AC:

2981

AN:

4816

European-Finnish (FIN)

AF:

0.657

AC:

6908

AN:

10508

Middle Eastern (MID)

AF:

0.755

AC:

222

AN:

294

European-Non Finnish (NFE)

AF:

0.704

AC:

47789

AN:

67924

Other (OTH)

AF:

0.606

AC:

1277

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1510

3021

4531

6042

7552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.609

Hom.:

13165

Bravo

AF:

0.517

Asia WGS

AF:

0.567

AC:

1972

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 06, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neurofibromatosis, type 1

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Neurofibromatosis, familial spinal

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

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

-0.83

CADD

Benign

3.9

(source)

DANN

Benign

0.69

PhyloP100

-0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over