17-31232043-ATTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTT

Position:

• chr17-31232043-ATTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001042492.3(NF1):​c.3198-5_3198-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (249 hom., cov: 0)
  • Exomes 𝑓: 0.039 (382 hom.)
• Consequence: NF1 NM_001042492.3 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.50

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-31232043-A-ATT is Benign according to our data. Variant chr17-31232043-A-ATT is described in ClinVar as [Likely_benign]. Clinvar id is 996535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3	c.3198-5_3198-4dupTT		splice_region_variant, intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.3198-5_3198-4dupTT		splice_region_variant, intron_variant			NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.3198-5_3198-4dupTT		splice_region_variant, intron_variant		1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 1986 AN: 90884 Hom.: 250 Cov.: 0

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00498

Gnomad EAS AF: 0.0246

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.00118

Gnomad MID AF: 0.00510

Gnomad NFE AF: 0.00733

Gnomad OTH AF: 0.0197

GnomAD3 exomes AF: 0.0492 AC: 3200 AN: 65012 Hom.: 154 AF XY: 0.0484 AC XY: 1693 AN XY: 34954

Gnomad AFR exome AF: 0.0860

Gnomad AMR exome AF: 0.0925

Gnomad ASJ exome AF: 0.0314

Gnomad EAS exome AF: 0.109

Gnomad SAS exome AF: 0.0433

Gnomad FIN exome AF: 0.00480

Gnomad NFE exome AF: 0.0415

Gnomad OTH exome AF: 0.0544

GnomAD4 exome AF: 0.0394 AC: 19552 AN: 496486 Hom.: 382 Cov.: 4 AF XY: 0.0428 AC XY: 11174 AN XY: 260774

Gnomad4 AFR exome AF: 0.0495

Gnomad4 AMR exome AF: 0.0714

Gnomad4 ASJ exome AF: 0.0343

Gnomad4 EAS exome AF: 0.0639

Gnomad4 SAS exome AF: 0.0797

Gnomad4 FIN exome AF: 0.0296

Gnomad4 NFE exome AF: 0.0323

Gnomad4 OTH exome AF: 0.0423

GnomAD4 genome AF: 0.0219 AC: 1987 AN: 90880 Hom.: 249 Cov.: 0 AF XY: 0.0219 AC XY: 920 AN XY: 42032

Gnomad4 AFR AF: 0.0610

Gnomad4 AMR AF: 0.0163

Gnomad4 ASJ AF: 0.00498

Gnomad4 EAS AF: 0.0251

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.00118

Gnomad4 NFE AF: 0.00733

Gnomad4 OTH AF: 0.0196

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neurofibromatosis, type 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Mar 15, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, The Hospital for Sick Children	Oct 26, 2020	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Aug 15, 2023

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs371047262; hg19: chr17-29559061;