rs2952976

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001042492.3(NF1):c.288+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 1,357,778 control chromosomes in the GnomAD database, including 303,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 27064 hom., cov: 31)

Exomes 𝑓: 0.67 ( 276728 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.416

Publications

19 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=-0.88).

BP6

Variant 17-31159134-G-A is Benign according to our data. Variant chr17-31159134-G-A is described in ClinVar as Benign. ClinVar VariationId is 257283.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.288+41G>A	intron_variant	Intron 3 of 57	ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.4 link	c.288+41G>A	intron_variant	Intron 3 of 56		NP_000258.1	P21359-2
NF1	NM_001128147.3 link	c.288+41G>A	intron_variant	Intron 3 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.288+41G>A		intron_variant	Intron 3 of 57	1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86567

AN:

151810

Hom.:

27057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.769

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.655

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.629

GnomAD2 exomes

AF:

0.626

AC:

155285

AN:

247996

AF XY:

0.641

show subpopulations

Gnomad AFR exome

AF:

0.291

Gnomad AMR exome

AF:

0.507

Gnomad ASJ exome

AF:

0.777

Gnomad EAS exome

AF:

0.561

Gnomad FIN exome

AF:

0.660

Gnomad NFE exome

AF:

0.698

Gnomad OTH exome

AF:

0.672

GnomAD4 exome

AF:

0.672

AC:

810843

AN:

1205850

Hom.:

276728

Cov.:

AF XY:

0.674

AC XY:

412683

AN XY:

612440

show subpopulations

African (AFR)

AF:

0.291

AC:

8259

AN:

28344

American (AMR)

AF:

0.516

AC:

22754

AN:

44126

Ashkenazi Jewish (ASJ)

AF:

0.775

AC:

18978

AN:

24496

East Asian (EAS)

AF:

0.555

AC:

21233

AN:

38256

South Asian (SAS)

AF:

0.633

AC:

51211

AN:

80860

European-Finnish (FIN)

AF:

0.655

AC:

34558

AN:

52740

Middle Eastern (MID)

AF:

0.770

AC:

4038

AN:

5244

European-Non Finnish (NFE)

AF:

0.699

AC:

615168

AN:

879952

Other (OTH)

AF:

0.668

AC:

34644

AN:

51832

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

13117

26234

39352

52469

65586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13994

27988

41982

55976

69970

<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:

0.570

AC:

86607

AN:

151928

Hom.:

27064

Cov.:

AF XY:

0.567

AC XY:

42075

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.303

AC:

12555

AN:

41462

American (AMR)

AF:

0.565

AC:

8620

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.769

AC:

2667

AN:

3468

East Asian (EAS)

AF:

0.560

AC:

2898

AN:

5172

South Asian (SAS)

AF:

0.620

AC:

2988

AN:

4816

European-Finnish (FIN)

AF:

0.655

AC:

6906

AN:

10540

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.704

AC:

47761

AN:

67890

Other (OTH)

AF:

0.630

AC:

1330

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1694

3388

5081

6775

8469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.612

Hom.:

8817

Bravo

AF:

0.553

Asia WGS

AF:

0.578

AC:

2011

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

- -

Sep 14, 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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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. -

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

-0.88

CADD

Benign

(source)

DANN

Benign

0.52

PhyloP100

0.42

PromoterAI

0.0047

Neutral

(source)

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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