17-31349086-CTTGTTTGTTTGTTTGT-CTTGTTTGT

Variant summary

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

The NM_001042492.3(NF1):c.7190-15_7190-8del variant causes a intron change. The variant allele was found at a frequency of 0.00018 in 1,550,918 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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-CTTGTTTGT-C is Benign according to our data. Variant chr17-31349086-CTTGTTTGT-C is described in ClinVar as [Likely_benign]. Clinvar id is 422181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3	c.7190-15_7190-8del		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.7127-15_7127-8del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.7190-15_7190-8del		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 151960 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000142 AC: 22 AN: 154686 Hom.: 0 AF XY: 0.0000979 AC XY: 8 AN XY: 81712

Gnomad AFR exome AF: 0.000109

Gnomad AMR exome AF: 0.000247

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000176

Gnomad SAS exome AF: 0.000134

Gnomad FIN exome AF: 0.0000789

Gnomad NFE exome AF: 0.000145

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000182 AC: 255 AN: 1398844 Hom.: 1 AF XY: 0.000177 AC XY: 122 AN XY: 690820

Gnomad4 AFR exome AF: 0.0000632

Gnomad4 AMR exome AF: 0.000250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000167

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.000126

Gnomad4 NFE exome AF: 0.000194

Gnomad4 OTH exome AF: 0.000121

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152074 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74342

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000155

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Dec 12, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 14, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, criteria provided, single submitter

curation

Sema4, Sema4

Mar 11, 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;