17-31349086-CTTGTTTGTTTGTTTGT-CTTGTTTGTTTGTTTGTTTGT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001042492.3(NF1):c.7190-11_7190-8dup variant causes a intron change. The variant allele was found at a frequency of 0.000841 in 1,550,920 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (2 hom.)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 4.75

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 17-31349086-C-CTTGT is Benign according to our data. Variant chr17-31349086-C-CTTGT is described in ClinVar as [Likely_benign]. Clinvar id is 560800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 257 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3	c.7190-11_7190-8dup		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.7127-11_7127-8dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.7190-11_7190-8dup		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.00169 AC: 257 AN: 151960 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00443

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000567

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00105 AC: 162 AN: 154686 Hom.: 0 AF XY: 0.000844 AC XY: 69 AN XY: 81712

Gnomad AFR exome AF: 0.00525

Gnomad AMR exome AF: 0.000783

Gnomad ASJ exome AF: 0.00192

Gnomad EAS exome AF: 0.00141

Gnomad SAS exome AF: 0.000447

Gnomad FIN exome AF: 0.000710

Gnomad NFE exome AF: 0.000627

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000748 AC: 1046 AN: 1398846 Hom.: 2 Cov.: 31 AF XY: 0.000715 AC XY: 494 AN XY: 690820

Gnomad4 AFR exome AF: 0.00512

Gnomad4 AMR exome AF: 0.000528

Gnomad4 ASJ exome AF: 0.00191

Gnomad4 EAS exome AF: 0.000722

Gnomad4 SAS exome AF: 0.000841

Gnomad4 FIN exome AF: 0.000420

Gnomad4 NFE exome AF: 0.000580

Gnomad4 OTH exome AF: 0.00128

GnomAD4 genome AF: 0.00170 AC: 259 AN: 152074 Hom.: 0 Cov.: 32 AF XY: 0.00148 AC XY: 110 AN XY: 74342

Gnomad4 AFR AF: 0.00446

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000567

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.00142

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neurofibromatosis, type 1 Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Mar 15, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Nov 06, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, The Hospital for Sick Children	Oct 26, 2020	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Nov 20, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2022	This variant is associated with the following publications: (PMID: 30308447, 34426522) -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	NF1: BP4, BS1, BS2 -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Mar 30, 2023

- -

Hereditary cancer-predisposing syndrome Benign:1

Benign, criteria provided, single submitter

curation

Sema4, Sema4

Dec 07, 2021

- -

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: rs149197458; hg19: chr17-29676104;