Variant rs2953000 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.888+108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 1,034,132 control chromosomes in the GnomAD database, including 223,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 26002 hom., cov: 33)

Exomes 𝑓: 0.66 ( 197670 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.209

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 17-31182773-C-T is Benign according to our data. Variant chr17-31182773-C-T is described in ClinVar as [Benign]. Clinvar id is 561465.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	Protein	UniProt
NF1	NM_001042492.3 link	c.888+108C>T	intron_variant	ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.3 link	c.888+108C>T	intron_variant		NP_000258.1	P21359-2
NF1	NM_001128147.3 link	c.888+108C>T	intron_variant		NP_001121619.1	P21359-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9 link	c.888+108C>T		intron_variant		1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83639

AN:

151540

Hom.:

26005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.719

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.765

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.617

Gnomad FIN

AF:

0.653

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.616

GnomAD4 exome

AF:

0.661

AC:

583581

AN:

882474

Hom.:

197670

Cov.:

AF XY:

0.663

AC XY:

301109

AN XY:

454342

show subpopulations

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.517

Gnomad4 ASJ exome

AF:

0.772

Gnomad4 EAS exome

AF:

0.458

Gnomad4 SAS exome

AF:

0.631

Gnomad4 FIN exome

AF:

0.654

Gnomad4 NFE exome

AF:

0.695

Gnomad4 OTH exome

AF:

0.655

GnomAD4 genome

AF:

0.552

AC:

83643

AN:

151658

Hom.:

26002

Cov.:

AF XY:

0.547

AC XY:

40573

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.557

Gnomad4 ASJ

AF:

0.765

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.616

Gnomad4 FIN

AF:

0.653

Gnomad4 NFE

AF:

0.703

Gnomad4 OTH

AF:

0.616

Alfa

AF:

0.597

Hom.:

4295

Bravo

AF:

0.533

Asia WGS

AF:

0.530

AC:

1842

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.81

CADD

Benign

5.6

DANN

Benign

0.59

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