Variant 17-31232043-ATTTTTTTTTTTTTTT-ATTTTTTTTTTTTTT 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.3198-4delT 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 0.015 ( 9 hom., cov: 0)

Exomes 𝑓: 0.044 ( 2 hom. )

Consequence

NF1
NM_001042492.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

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-AT-A is Benign according to our data. Variant chr17-31232043-AT-A is described in ClinVar as [Benign]. Clinvar id is 996534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-31232043-AT-A is described in Lovd as [Benign]. Variant chr17-31232043-AT-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0709 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.3198-4delT		splice_region_variant, intron_variant		ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.3 linkuse as main transcript	c.3198-4delT		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.3198-4delT		splice_region_variant, intron_variant		1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

1335

AN:

90878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0325

Gnomad AMI

AF:

0.0118

Gnomad AMR

AF:

0.00971

Gnomad ASJ

AF:

0.00919

Gnomad EAS

AF:

0.00220

Gnomad SAS

AF:

0.0317

Gnomad FIN

AF:

0.00473

Gnomad MID

AF:

0.0204

Gnomad NFE

AF:

0.00798

Gnomad OTH

AF:

0.0164

GnomAD3 exomes

AF:

0.0294

AC:

1910

AN:

65012

Hom.:

AF XY:

0.0276

AC XY:

966

AN XY:

34954

show subpopulations

Gnomad AFR exome

AF:

0.0512

Gnomad AMR exome

AF:

0.0617

Gnomad ASJ exome

AF:

0.0308

Gnomad EAS exome

AF:

0.0310

Gnomad SAS exome

AF:

0.0252

Gnomad FIN exome

AF:

0.00183

Gnomad NFE exome

AF:

0.0268

Gnomad OTH exome

AF:

0.0430

GnomAD4 exome

AF:

0.0442

AC:

21769

AN:

492098

Hom.:

Cov.:

AF XY:

0.0471

AC XY:

12169

AN XY:

258232

show subpopulations

Gnomad4 AFR exome

AF:

0.0464

Gnomad4 AMR exome

AF:

0.0486

Gnomad4 ASJ exome

AF:

0.0562

Gnomad4 EAS exome

AF:

0.0743

Gnomad4 SAS exome

AF:

0.0418

Gnomad4 FIN exome

AF:

0.0387

Gnomad4 NFE exome

AF:

0.0421

Gnomad4 OTH exome

AF:

0.0543

GnomAD4 genome

AF:

0.0147

AC:

1336

AN:

90874

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

664

AN XY:

42024

show subpopulations

Gnomad4 AFR

AF:

0.0325

Gnomad4 AMR

AF:

0.00970

Gnomad4 ASJ

AF:

0.00919

Gnomad4 EAS

AF:

0.00221

Gnomad4 SAS

AF:

0.0318

Gnomad4 FIN

AF:

0.00473

Gnomad4 NFE

AF:

0.00798

Gnomad4 OTH

AF:

0.0163

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 09, 2023	- -

Neurofibromatosis, type 1

Benign:2

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 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