17-31232043-ATTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTT

Position:

• chr17-31232043-ATTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6_Very_Strong BS2_Supporting

The NM_001042492.3(NF1):​c.3198-7_3198-4dupTTTT 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 0.00034 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0033 (15 hom.)
• Consequence: NF1 NM_001042492.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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 -9 ACMG points.

• BP6: Variant 17-31232043-A-ATTTT is Benign according to our data. Variant chr17-31232043-A-ATTTT is described in ClinVar as [Likely_benign]. Clinvar id is 1217106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 31 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3	c.3198-7_3198-4dupTTTT		splice_region_variant, intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.3198-7_3198-4dupTTTT		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.3198-7_3198-4dupTTTT		splice_region_variant, intron_variant		1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.000341 AC: 31 AN: 90906 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000424

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000146

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00546 AC: 355 AN: 65012 Hom.: 6 AF XY: 0.00509 AC XY: 178 AN XY: 34954

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.00314

Gnomad EAS exome AF: 0.0115

Gnomad SAS exome AF: 0.00486

Gnomad FIN exome AF: 0.00126

Gnomad NFE exome AF: 0.00361

Gnomad OTH exome AF: 0.00657

GnomAD4 exome AF: 0.00334 AC: 1667 AN: 498578 Hom.: 15 Cov.: 4 AF XY: 0.00354 AC XY: 927 AN XY: 262146

Gnomad4 AFR exome AF: 0.00631

Gnomad4 AMR exome AF: 0.00699

Gnomad4 ASJ exome AF: 0.00303

Gnomad4 EAS exome AF: 0.00369

Gnomad4 SAS exome AF: 0.00895

Gnomad4 FIN exome AF: 0.00271

Gnomad4 NFE exome AF: 0.00244

Gnomad4 OTH exome AF: 0.00348

GnomAD4 genome AF: 0.000341 AC: 31 AN: 90902 Hom.: 1 Cov.: 0 AF XY: 0.000404 AC XY: 17 AN XY: 42042

Gnomad4 AFR AF: 0.00102

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000425

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000146

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 07, 2020

- -

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;