Genetic Variant NF1:c.7190-11_7190-8dupGTTT (chr17-31349086-C-CTTGT) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001042492.3(NF1):c.7190-11_7190-8dupGTTT variant causes a splice region, 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 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 4.75

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0017 (259/152074) while in subpopulation AFR AF= 0.00446 (185/41442). AF 95% confidence interval is 0.00394. There are 0 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 259 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3 link	c.7190-11_7190-8dupGTTT		splice_region_variant, intron_variant	Intron 48 of 57	ENST00000358273.9	NP_001035957.1	P21359-1
NF1	NM_000267.3 link	c.7127-11_7127-8dupGTTT		splice_region_variant, intron_variant	Intron 47 of 56		NP_000258.1	P21359-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9 link	c.7190-34_7190-33insTTGT		intron_variant	Intron 48 of 57	1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.00169

AC:

257

AN:

151960

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.000844

AC XY:

AN XY:

81712

show subpopulations

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.:

Cov.:

AF XY:

0.000715

AC XY:

494

AN XY:

690820

show subpopulations

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.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74342

show subpopulations

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:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neurofibromatosis, type 1

Benign:3

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 06, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 26, 2020

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Nov 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 29, 2022

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30308447, 34426522) -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NF1: BP4, BS1, BS2 -

not specified

Benign:2

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 30, 2023

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Dec 07, 2021

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over