Variant 17-31232070-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001042492.3(NF1):c.3198-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.048 ( 0 hom., cov: 0)

Exomes 𝑓: 0.019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NF1
NM_001042492.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001181

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.140

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 17-31232070-C-T is Benign according to our data. Variant chr17-31232070-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 457630.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3 linkuse as main transcript	c.3198-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3 linkuse as main transcript	c.3198-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9 linkuse as main transcript	c.3198-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001042492.3	ENSP00000351015	P1	P21359-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1065

AN:

22372

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0365

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.0388

Gnomad ASJ

AF:

0.0537

Gnomad EAS

AF:

0.0419

Gnomad SAS

AF:

0.0254

Gnomad FIN

AF:

0.0243

Gnomad MID

AF:

0.0882

Gnomad NFE

AF:

0.0569

Gnomad OTH

AF:

0.0337

GnomAD3 exomes

AF:

0.00502

AC:

154

AN:

30650

Hom.:

AF XY:

0.00525

AC XY:

AN XY:

16370

show subpopulations

Gnomad AFR exome

AF:

0.00349

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.00363

Gnomad EAS exome

AF:

0.00505

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.00321

Gnomad NFE exome

AF:

0.00364

Gnomad OTH exome

AF:

0.00749

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0194

AC:

2456

AN:

126416

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

1303

AN XY:

65742

show subpopulations

Gnomad4 AFR exome

AF:

0.0119

Gnomad4 AMR exome

AF:

0.0263

Gnomad4 ASJ exome

AF:

0.0133

Gnomad4 EAS exome

AF:

0.00837

Gnomad4 SAS exome

AF:

0.0763

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.0182

Gnomad4 OTH exome

AF:

0.0201

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0476

AC:

1065

AN:

22374

Hom.:

Cov.:

AF XY:

0.0437

AC XY:

462

AN XY:

10566

show subpopulations

Gnomad4 AFR

AF:

0.0364

Gnomad4 AMR

AF:

0.0388

Gnomad4 ASJ

AF:

0.0537

Gnomad4 EAS

AF:

0.0421

Gnomad4 SAS

AF:

0.0258

Gnomad4 FIN

AF:

0.0243

Gnomad4 NFE

AF:

0.0569

Gnomad4 OTH

AF:

0.0337

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Neurofibromatosis, type 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 15, 2017

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 08, 2019

- -

Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.6

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0012

dbscSNV1_RF

Benign

0.19

SpliceAI score (max)

0.11

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