17-31336607-TAA-TA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001042492.3(NF1):c.6148-17del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000865 in 1,456,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000082 (0 hom.)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.877

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 17-31336607-TA-T is Benign according to our data. Variant chr17-31336607-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 3037932.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-31336607-TA-T is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3	c.6148-17del		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.6085-17del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.6148-17del		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.000127 AC: 19 AN: 149562 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000666

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000740

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000819 AC: 107 AN: 1306986 Hom.: 0 Cov.: 33 AF XY: 0.0000957 AC XY: 62 AN XY: 647922

Gnomad4 AFR exome AF: 0.000396

Gnomad4 AMR exome AF: 0.0000693

Gnomad4 ASJ exome AF: 0.0000856

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0000137

Gnomad4 FIN exome AF: 0.0000216

Gnomad4 NFE exome AF: 0.0000740

Gnomad4 OTH exome AF: 0.000111

GnomAD4 genome AF: 0.000127 AC: 19 AN: 149648 Hom.: 0 Cov.: 0 AF XY: 0.000110 AC XY: 8 AN XY: 72970

Gnomad4 AFR AF: 0.000320

Gnomad4 AMR AF: 0.0000666

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000740

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

NF1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 28, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs33925668; hg19: chr17-29663625;