Variant 17-31336607-TAA-TAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001042492.3(NF1):c.6148-19_6148-17dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,415,564 control chromosomes in the GnomAD database, including 38 homozygotes. Variant has been reported in ClinVar as Likely benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0076 ( 14 hom., cov: 0)

Exomes 𝑓: 0.012 ( 24 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.877

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:

NF1 (HGNC:):

NF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 17-31336607-T-TAAA is Benign according to our data. Variant chr17-31336607-T-TAAA is described in ClinVar as [Likely_benign]. Clinvar id is 1186284.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00764 (1143/149616) while in subpopulation SAS AF= 0.0109 (52/4752). AF 95% confidence interval is 0.01. There are 14 homozygotes in gnomad4. There are 579 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1143 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3 linkuse as main transcript	c.6148-19_6148-17dupAAA		intron_variant		ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.3 linkuse as main transcript	c.6085-19_6085-17dupAAA		intron_variant			NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9 linkuse as main transcript	c.6148-19_6148-17dupAAA		intron_variant		1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.00759

AC:

1135

AN:

149530

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00175

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.00520

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00195

Gnomad SAS

AF:

0.0111

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.00649

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00876

GnomAD3 exomes

AF:

0.0132

AC:

1842

AN:

139834

Hom.:

AF XY:

0.0134

AC XY:

1014

AN XY:

75790

show subpopulations

Gnomad AFR exome

AF:

0.00254

Gnomad AMR exome

AF:

0.00792

Gnomad ASJ exome

AF:

0.0220

Gnomad EAS exome

AF:

0.00290

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.0211

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.0156

GnomAD4 exome

AF:

0.0118

AC:

14896

AN:

1265948

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

7562

AN XY:

627486

show subpopulations

Gnomad4 AFR exome

AF:

0.00274

Gnomad4 AMR exome

AF:

0.00757

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.00623

Gnomad4 SAS exome

AF:

0.0131

Gnomad4 FIN exome

AF:

0.0182

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.0119

GnomAD4 genome

AF:

0.00764

AC:

1143

AN:

149616

Hom.:

Cov.:

AF XY:

0.00794

AC XY:

579

AN XY:

72956

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00519

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00195

Gnomad4 SAS

AF:

0.0109

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00868

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

6.0

Splicing

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