Variant 17-31260323-G-C 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.4431-46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 1,584,532 control chromosomes in the GnomAD database, including 3,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 276 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3442 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.448

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=-0.82).

BP6

Variant 17-31260323-G-C is Benign according to our data. Variant chr17-31260323-G-C is described in ClinVar as [Benign]. Clinvar id is 257290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-31260323-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0725 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.4431-46G>C		intron_variant		ENST00000358273.9
NF1	NM_000267.3 linkuse as main transcript	c.4368-46G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9 linkuse as main transcript	c.4431-46G>C		intron_variant		1	NM_001042492.3	P1	P21359-1

Frequencies

GnomAD3 genomes

AF:

0.0530

AC:

8059

AN:

152130

Hom.:

277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0384

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0742

Gnomad OTH

AF:

0.0588

GnomAD3 exomes

AF:

0.0529

AC:

13203

AN:

249388

Hom.:

438

AF XY:

0.0541

AC XY:

7305

AN XY:

134942

show subpopulations

Gnomad AFR exome

AF:

0.0124

Gnomad AMR exome

AF:

0.0275

Gnomad ASJ exome

AF:

0.0844

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0202

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0719

Gnomad OTH exome

AF:

0.0633

GnomAD4 exome

AF:

0.0659

AC:

94351

AN:

1432284

Hom.:

3442

Cov.:

AF XY:

0.0652

AC XY:

46587

AN XY:

714468

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.0301

Gnomad4 ASJ exome

AF:

0.0861

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0214

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.0731

Gnomad4 OTH exome

AF:

0.0599

GnomAD4 genome

AF:

0.0529

AC:

8059

AN:

152248

Hom.:

276

Cov.:

AF XY:

0.0540

AC XY:

4016

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0148

Gnomad4 AMR

AF:

0.0383

Gnomad4 ASJ

AF:

0.0844

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.0742

Gnomad4 OTH

AF:

0.0582

Alfa

AF:

0.0433

Hom.:

Bravo

AF:

0.0458

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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 13, 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

-0.82

Cadd

Benign

1.4

Dann

Benign

0.43

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