rs9894648

Variant summary

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

The NM_001042492.3(NF1):c.5268+23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,599,250 control chromosomes in the GnomAD database, including 312,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32442 hom., cov: 32)

Exomes 𝑓: 0.62 ( 279594 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00900

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:

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=-0.83).

BP6

Variant 17-31326275-T-C is Benign according to our data. Variant chr17-31326275-T-C is described in ClinVar as [Benign]. Clinvar id is 257293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-31326275-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3 linkuse as main transcript	c.5268+23T>C		intron_variant		ENST00000358273.9
NF1	NM_000267.3 linkuse as main transcript	c.5205+23T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9 linkuse as main transcript	c.5268+23T>C		intron_variant		1	NM_001042492.3	P1	P21359-1

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98310

AN:

151888

Hom.:

32416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.749

Gnomad AMI

AF:

0.697

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.704

Gnomad EAS

AF:

0.447

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.634

Gnomad OTH

AF:

0.651

GnomAD3 exomes

AF:

0.591

AC:

140307

AN:

237330

Hom.:

42754

AF XY:

0.601

AC XY:

77761

AN XY:

129426

show subpopulations

Gnomad AFR exome

AF:

0.753

Gnomad AMR exome

AF:

0.413

Gnomad ASJ exome

AF:

0.704

Gnomad EAS exome

AF:

0.441

Gnomad SAS exome

AF:

0.625

Gnomad FIN exome

AF:

0.618

Gnomad NFE exome

AF:

0.625

Gnomad OTH exome

AF:

0.608

GnomAD4 exome

AF:

0.619

AC:

895405

AN:

1447244

Hom.:

279594

Cov.:

AF XY:

0.620

AC XY:

446658

AN XY:

720492

show subpopulations

Gnomad4 AFR exome

AF:

0.759

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.706

Gnomad4 EAS exome

AF:

0.473

Gnomad4 SAS exome

AF:

0.628

Gnomad4 FIN exome

AF:

0.610

Gnomad4 NFE exome

AF:

0.624

Gnomad4 OTH exome

AF:

0.623

GnomAD4 genome

AF:

0.647

AC:

98373

AN:

152006

Hom.:

32442

Cov.:

AF XY:

0.642

AC XY:

47685

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.749

Gnomad4 AMR

AF:

0.510

Gnomad4 ASJ

AF:

0.704

Gnomad4 EAS

AF:

0.446

Gnomad4 SAS

AF:

0.618

Gnomad4 FIN

AF:

0.620

Gnomad4 NFE

AF:

0.634

Gnomad4 OTH

AF:

0.647

Alfa

AF:

0.643

Hom.:

5860

Bravo

AF:

0.643

Asia WGS

AF:

0.527

AC:

1831

AN:

3478

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 10, 2018	- -

Neurofibromatosis, type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2018

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

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

-0.83

Cadd

Benign

2.3

Dann

Benign

0.41

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