17-31336607-TAA-TA

Variant names:

• chr17-31336607-TA-T
• rs33925668
• NM_001042492.3:c.6148-17delA

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP6_Moderate BS2_Supporting

The NM_001042492.3(NF1):​c.6148-17delA 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 (★). There are indicators that this mutation may affect the branch point..

• 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:2
• 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 -3 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 GnomAd4 at 19 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 rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.6148-17delA		intron_variant	Intron 41 of 57	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.6085-17delA		intron_variant	Intron 40 of 56		NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.6148-27delA		intron_variant	Intron 41 of 57	1	NM_001042492.3	ENSP00000351015.4

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:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

NF1-related disorder Benign:1

Nov 28, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		5.0

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;