rs7405740

Variant names:

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.7189+37C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 1,544,818 control chromosomes in the GnomAD database, including 644,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59692 hom., cov: 32)

Exomes 𝑓: 0.92 ( 584630 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.43

Publications

20 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 17-31343172-C-G is Benign according to our data. Variant chr17-31343172-C-G is described in ClinVar as Benign. ClinVar VariationId is 257300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3 link	c.7189+37C>G		intron_variant	Intron 48 of 57	ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.4 link	c.7126+37C>G		intron_variant	Intron 47 of 56		NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9 link	c.7189+37C>G		intron_variant	Intron 48 of 57	1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.884

AC:

134465

AN:

152130

Hom.:

59658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.800

Gnomad AMI

AF:

0.954

Gnomad AMR

AF:

0.878

Gnomad ASJ

AF:

0.919

Gnomad EAS

AF:

0.891

Gnomad SAS

AF:

0.952

Gnomad FIN

AF:

0.950

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.918

Gnomad OTH

AF:

0.870

GnomAD2 exomes

AF:

0.907

AC:

221128

AN:

243688

AF XY:

0.912

show subpopulations

Gnomad AFR exome

AF:

0.799

Gnomad AMR exome

AF:

0.887

Gnomad ASJ exome

AF:

0.914

Gnomad EAS exome

AF:

0.881

Gnomad FIN exome

AF:

0.944

Gnomad NFE exome

AF:

0.915

Gnomad OTH exome

AF:

0.901

GnomAD4 exome

AF:

0.916

AC:

1275297

AN:

1392570

Hom.:

584630

Cov.:

AF XY:

0.917

AC XY:

639141

AN XY:

696714

show subpopulations

African (AFR)

AF:

0.795

AC:

25486

AN:

32044

American (AMR)

AF:

0.886

AC:

39333

AN:

44400

Ashkenazi Jewish (ASJ)

AF:

0.918

AC:

23550

AN:

25664

East Asian (EAS)

AF:

0.925

AC:

36372

AN:

39338

South Asian (SAS)

AF:

0.949

AC:

80315

AN:

84616

European-Finnish (FIN)

AF:

0.945

AC:

48564

AN:

51388

Middle Eastern (MID)

AF:

0.869

AC:

4873

AN:

5610

European-Non Finnish (NFE)

AF:

0.917

AC:

964456

AN:

1051442

Other (OTH)

AF:

0.901

AC:

52348

AN:

58068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4892

9783

14675

19566

24458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19914

39828

59742

79656

99570

<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:

0.884

AC:

134554

AN:

152248

Hom.:

59692

Cov.:

AF XY:

0.888

AC XY:

66078

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.801

AC:

33234

AN:

41516

American (AMR)

AF:

0.877

AC:

13419

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.919

AC:

3190

AN:

3472

East Asian (EAS)

AF:

0.891

AC:

4615

AN:

5180

South Asian (SAS)

AF:

0.952

AC:

4599

AN:

4830

European-Finnish (FIN)

AF:

0.950

AC:

10084

AN:

10614

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.918

AC:

62472

AN:

68024

Other (OTH)

AF:

0.867

AC:

1832

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

795

1590

2386

3181

3976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<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:

0.902

Hom.:

11384

Bravo

AF:

0.872

Asia WGS

AF:

0.898

AC:

3120

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 10, 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

-0.88

CADD

Benign

1.3

(source)

DANN

Benign

0.69

PhyloP100

-1.4

PromoterAI

0.0025

Neutral

(source)

Mutation Taster

=17/83

disease causing

(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