Variant 17-31232043-ATTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001042492.3(NF1):c.3198-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4359 hom., cov: 0)

Exomes 𝑓: 0.096 ( 2286 hom. )

Consequence

NF1
NM_001042492.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.50

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 links:

NF1 (HGNC:):

NF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 17-31232043-A-AT is Benign according to our data. Variant chr17-31232043-A-AT is described in ClinVar as [Benign]. Clinvar id is 803349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3 linkuse as main transcript	c.3198-4dupT		splice_region_variant, intron_variant		ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.3 linkuse as main transcript	c.3198-4dupT		splice_region_variant, intron_variant			NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9 linkuse as main transcript	c.3198-4dupT		splice_region_variant, intron_variant		1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

19937

AN:

90834

Hom.:

4358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.0479

Gnomad MID

AF:

0.0561

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.109

AC:

7082

AN:

65012

Hom.:

769

AF XY:

0.104

AC XY:

3642

AN XY:

34954

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.0768

Gnomad EAS exome

AF:

0.240

Gnomad SAS exome

AF:

0.0980

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0924

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.0963

AC:

47760

AN:

496024

Hom.:

2286

Cov.:

AF XY:

0.105

AC XY:

27331

AN XY:

260534

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.0982

Gnomad4 EAS exome

AF:

0.174

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.0799

Gnomad4 NFE exome

AF:

0.0824

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.219

AC:

19935

AN:

90830

Hom.:

4359

Cov.:

AF XY:

0.210

AC XY:

8829

AN XY:

42006

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.191

Gnomad4 EAS

AF:

0.303

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.0479

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.180

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neurofibromatosis, type 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, The Hospital for Sick Children	Oct 26, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Mar 15, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over