NM_001042492.3:c.3198-7_3198-4dupTTTT

Variant names:

• chr17-31232043-A-ATTTT
• rs371047262
• NM_001042492.3:c.3198-7_3198-4dupTTTT

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP6_Very_Strong BS1 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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• neurofibromatosis type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
• neurofibromatosis-Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
• Moyamoya disease

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 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 VariationId is 1217106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00334 (1667/498578) while in subpopulation SAS AF = 0.00895 (384/42898). AF 95% confidence interval is 0.00821. There are 15 homozygotes in GnomAdExome4. There are 927 alleles in the male GnomAdExome4 subpopulation. Median coverage is 4. This position passed quality control check.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042492.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	NM_001042492.3	MANE Select	c.3198-7_3198-4dupTTTT		splice_region intron	N/A	NP_001035957.1
	NF1	NM_000267.4		c.3198-7_3198-4dupTTTT		splice_region intron	N/A	NP_000258.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	ENST00000358273.9	TSL:1 MANE Select	c.3198-30_3198-29insTTTT		intron	N/A	ENSP00000351015.4
	NF1	ENST00000356175.7	TSL:1	c.3198-30_3198-29insTTTT		intron	N/A	ENSP00000348498.3
	NF1	ENST00000579081.6	TSL:1	n.3198-30_3198-29insTTTT		intron	N/A	ENSP00000462408.2

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

GnomAD2 exomes AF: 0.00546 AC: 355 AN: 65012 AF XY: 0.00509

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 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

African (AFR) AF: 0.00631 AC: 64 AN: 10142

American (AMR) AF: 0.00699 AC: 112 AN: 16014

Ashkenazi Jewish (ASJ) AF: 0.00303 AC: 37 AN: 12220

East Asian (EAS) AF: 0.00369 AC: 62 AN: 16780

South Asian (SAS) AF: 0.00895 AC: 384 AN: 42898

European-Finnish (FIN) AF: 0.00271 AC: 78 AN: 28834

Middle Eastern (MID) AF: 0.00297 AC: 5 AN: 1682

European-Non Finnish (NFE) AF: 0.00244 AC: 849 AN: 348178

Other (OTH) AF: 0.00348 AC: 76 AN: 21830

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

African (AFR) AF: 0.00102 AC: 23 AN: 22460

American (AMR) AF: 0.00 AC: 0 AN: 7430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2612

East Asian (EAS) AF: 0.00 AC: 0 AN: 2712

South Asian (SAS) AF: 0.000425 AC: 1 AN: 2352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 174

European-Non Finnish (NFE) AF: 0.000146 AC: 7 AN: 47880

Other (OTH) AF: 0.00 AC: 0 AN: 1226

Alfa AF: 0.000535 Hom.: 224

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

not provided Benign:1

Jan 07, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs371047262; hg19: chr17-29559061;