Variant chr17-31218969-A-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001042492.3(NF1):c.1528-29dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,531,434 control chromosomes in the GnomAD database, including 342,313 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27459 hom., cov: 0)

Exomes 𝑓: 0.67 ( 314854 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.685

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 -16 ACMG points.

BP6

Variant 17-31218969-A-AT is Benign according to our data. Variant chr17-31218969-A-AT is described in ClinVar as [Benign]. Clinvar id is 257277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
NF1	NM_001042492.3 linkuse as main transcript	c.1528-29dup	intron_variant	ENST00000358273.9
NF1	NM_000267.3 linkuse as main transcript	c.1528-29dup	intron_variant
NF1	NM_001128147.3 linkuse as main transcript	c.1528-29dup	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9 linkuse as main transcript	c.1528-29dup		intron_variant		1	NM_001042492.3	P1	P21359-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87645

AN:

151654

Hom.:

27452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.719

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.768

Gnomad EAS

AF:

0.562

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.705

Gnomad OTH

AF:

0.638

GnomAD3 exomes

AF:

0.626

AC:

120735

AN:

192966

Hom.:

38909

AF XY:

0.638

AC XY:

66178

AN XY:

103764

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.509

Gnomad ASJ exome

AF:

0.777

Gnomad EAS exome

AF:

0.560

Gnomad SAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.660

Gnomad NFE exome

AF:

0.694

Gnomad OTH exome

AF:

0.675

GnomAD4 exome

AF:

0.671

AC:

926025

AN:

1379662

Hom.:

314854

Cov.:

AF XY:

0.672

AC XY:

460726

AN XY:

685188

show subpopulations

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.517

Gnomad4 ASJ exome

AF:

0.773

Gnomad4 EAS exome

AF:

0.552

Gnomad4 SAS exome

AF:

0.631

Gnomad4 FIN exome

AF:

0.655

Gnomad4 NFE exome

AF:

0.693

Gnomad4 OTH exome

AF:

0.665

GnomAD4 genome

AF:

0.578

AC:

87686

AN:

151772

Hom.:

27459

Cov.:

AF XY:

0.574

AC XY:

42552

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.568

Gnomad4 ASJ

AF:

0.768

Gnomad4 EAS

AF:

0.561

Gnomad4 SAS

AF:

0.620

Gnomad4 FIN

AF:

0.657

Gnomad4 NFE

AF:

0.705

Gnomad4 OTH

AF:

0.638

Alfa

AF:

0.604

Hom.:

3783

Bravo

AF:

0.559

Asia WGS

AF:

0.579

AC:

2014

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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