Variant rs2066736 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.3496+33C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,612,700 control chromosomes in the GnomAD database, including 93,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13872 hom., cov: 31)

Exomes 𝑓: 0.32 ( 79404 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.204

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=-0.86).

BP6

Variant 17-31232914-C-A is Benign according to our data. Variant chr17-31232914-C-A is described in ClinVar as [Benign]. Clinvar id is 257285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-31232914-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3 link	c.3496+33C>A		intron_variant		ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.3 link	c.3496+33C>A		intron_variant			NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9 link	c.3496+33C>A		intron_variant		1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61271

AN:

151822

Hom.:

13847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.611

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.344

GnomAD3 exomes

AF:

0.365

AC:

91091

AN:

249686

Hom.:

17902

AF XY:

0.351

AC XY:

47444

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.616

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.437

Gnomad SAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.300

Gnomad OTH exome

AF:

0.324

GnomAD4 exome

AF:

0.322

AC:

469868

AN:

1460760

Hom.:

79404

Cov.:

AF XY:

0.321

AC XY:

233103

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.622

Gnomad4 AMR exome

AF:

0.477

Gnomad4 ASJ exome

AF:

0.225

Gnomad4 EAS exome

AF:

0.444

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.300

Gnomad4 OTH exome

AF:

0.324

GnomAD4 genome

AF:

0.404

AC:

61346

AN:

151940

Hom.:

13872

Cov.:

AF XY:

0.408

AC XY:

30275

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.611

Gnomad4 AMR

AF:

0.426

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.439

Gnomad4 SAS

AF:

0.374

Gnomad4 FIN

AF:

0.344

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.343

Alfa

AF:

0.252

Hom.:

920

Bravo

AF:

0.417

Asia WGS

AF:

0.416

AC:

1448

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

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	Jul 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.0

DANN

Benign

0.61

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