rs2285894

Positions:

chr17-31327858-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001042492.3(NF1):c.5609+19T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,605,644 control chromosomes in the GnomAD database, including 278,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 20825 hom., cov: 31)

Exomes 𝑓: 0.59 ( 257261 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -1.06

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-31327858-T-A is Benign according to our data. Variant chr17-31327858-T-A is described in ClinVar as [Benign]. Clinvar id is 257294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-31327858-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 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.5609+19T>A		intron_variant		ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.3 linkuse as main transcript	c.5546+19T>A		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.5609+19T>A		intron_variant		1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76225

AN:

151886

Hom.:

20816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.684

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.601

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.531

GnomAD3 exomes

AF:

0.535

AC:

133633

AN:

249712

Hom.:

37686

AF XY:

0.551

AC XY:

74557

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.377

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.356

Gnomad SAS exome

AF:

0.572

Gnomad FIN exome

AF:

0.600

Gnomad NFE exome

AF:

0.611

Gnomad OTH exome

AF:

0.567

GnomAD4 exome

AF:

0.589

AC:

856724

AN:

1453640

Hom.:

257261

Cov.:

AF XY:

0.591

AC XY:

427869

AN XY:

723682

show subpopulations

Gnomad4 AFR exome

AF:

0.280

Gnomad4 AMR exome

AF:

0.388

Gnomad4 ASJ exome

AF:

0.687

Gnomad4 EAS exome

AF:

0.375

Gnomad4 SAS exome

AF:

0.576

Gnomad4 FIN exome

AF:

0.596

Gnomad4 NFE exome

AF:

0.614

Gnomad4 OTH exome

AF:

0.573

GnomAD4 genome

AF:

0.502

AC:

76260

AN:

152004

Hom.:

20825

Cov.:

AF XY:

0.499

AC XY:

37069

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.294

Gnomad4 AMR

AF:

0.446

Gnomad4 ASJ

AF:

0.684

Gnomad4 EAS

AF:

0.358

Gnomad4 SAS

AF:

0.561

Gnomad4 FIN

AF:

0.601

Gnomad4 NFE

AF:

0.619

Gnomad4 OTH

AF:

0.528

Alfa

AF:

0.569

Hom.:

4707

Bravo

AF:

0.480

Asia WGS

AF:

0.438

AC:

1523

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2015	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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 25, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 12, 2016	Variant summary: The NF1 c.5546+19T>A variant involves the alteration of a non-conserved intronic nucleotide with 5/5 splice prediction tools calculating no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 64462/120180 (18196 homozygotes, frequency: 0.5363788), which suggests that the variant of interest is the major allele (most common allele observed in the general population. Therefore, the variant of interest is classified as Benign. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Neurofibromatosis, type 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Neurofibromatosis, familial spinal

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.21

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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