rs779081215

Variant names:

• chr17-31349113-T-G
• rs779081215
• NM_001042492.3:c.7190-7T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BS2_Supporting

The NM_001042492.3(NF1):​c.7190-7T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000842 in 1,424,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: NF1 NM_001042492.3 splice_region, intron
• Scores: Splicing: ADA: 0.001544
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.30
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 17-31349113-T-G is Benign according to our data. Variant chr17-31349113-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 412986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAdExome4 at 12 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.7190-7T>G		splice_region_variant, intron_variant	Intron 48 of 57	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.4	c.7127-7T>G		splice_region_variant, intron_variant	Intron 47 of 56		NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.7190-7T>G		splice_region_variant, intron_variant	Intron 48 of 57	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000102 AC: 2 AN: 197002 AF XY: 0.00000949

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000120

Gnomad OTH exome AF: 0.000193

GnomAD4 exome AF: 0.00000842 AC: 12 AN: 1424348 Hom.: 0 Cov.: 32 AF XY: 0.00000850 AC XY: 6 AN XY: 705498

African (AFR) AF: 0.00 AC: 0 AN: 32426

American (AMR) AF: 0.0000258 AC: 1 AN: 38760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25596

East Asian (EAS) AF: 0.00 AC: 0 AN: 37880

South Asian (SAS) AF: 0.00 AC: 0 AN: 81846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50930

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5714

European-Non Finnish (NFE) AF: 0.00000916 AC: 10 AN: 1092162

Other (OTH) AF: 0.00 AC: 0 AN: 59034

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neurofibromatosis, type 1 Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.86
PhyloP100		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0015
dbscSNV1_RF	Benign	0.056
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

Other links and lift over

dbSNP: rs779081215; hg19: chr17-29676131;