Variant rs2952976 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001042492.3(NF1):c.288+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 1,357,778 control chromosomes in the GnomAD database, including 303,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 27064 hom., cov: 31)

Exomes 𝑓: 0.67 ( 276728 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.416

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=-0.88).

BP6

Variant 17-31159134-G-A is Benign according to our data. Variant chr17-31159134-G-A is described in ClinVar as [Benign]. Clinvar id is 257283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
NF1	NM_001042492.3 linkuse as main transcript	c.288+41G>A	intron_variant	ENST00000358273.9
NF1	NM_000267.3 linkuse as main transcript	c.288+41G>A	intron_variant
NF1	NM_001128147.3 linkuse as main transcript	c.288+41G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9 linkuse as main transcript	c.288+41G>A		intron_variant		1	NM_001042492.3	P1	P21359-1

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86567

AN:

151810

Hom.:

27057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.769

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.655

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.629

GnomAD3 exomes

AF:

0.626

AC:

155285

AN:

247996

Hom.:

50315

AF XY:

0.641

AC XY:

86084

AN XY:

134260

show subpopulations

Gnomad AFR exome

AF:

0.291

Gnomad AMR exome

AF:

0.507

Gnomad ASJ exome

AF:

0.777

Gnomad EAS exome

AF:

0.561

Gnomad SAS exome

AF:

0.630

Gnomad FIN exome

AF:

0.660

Gnomad NFE exome

AF:

0.698

Gnomad OTH exome

AF:

0.672

GnomAD4 exome

AF:

0.672

AC:

810843

AN:

1205850

Hom.:

276728

Cov.:

AF XY:

0.674

AC XY:

412683

AN XY:

612440

show subpopulations

Gnomad4 AFR exome

AF:

0.291

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.775

Gnomad4 EAS exome

AF:

0.555

Gnomad4 SAS exome

AF:

0.633

Gnomad4 FIN exome

AF:

0.655

Gnomad4 NFE exome

AF:

0.699

Gnomad4 OTH exome

AF:

0.668

GnomAD4 genome

AF:

0.570

AC:

86607

AN:

151928

Hom.:

27064

Cov.:

AF XY:

0.567

AC XY:

42075

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.303

Gnomad4 AMR

AF:

0.565

Gnomad4 ASJ

AF:

0.769

Gnomad4 EAS

AF:

0.560

Gnomad4 SAS

AF:

0.620

Gnomad4 FIN

AF:

0.655

Gnomad4 NFE

AF:

0.704

Gnomad4 OTH

AF:

0.630

Alfa

AF:

0.592

Hom.:

4203

Bravo

AF:

0.553

Asia WGS

AF:

0.578

AC:

2011

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	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Neurofibromatosis, type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Neurofibromatosis, familial spinal

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

Dann

Benign

0.52

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