rs7405740

Positions:

• chr17-31343172-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001042492.3(NF1):​c.7189+37C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 1,544,818 control chromosomes in the GnomAD database, including 644,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59692 hom., cov: 32)
  • Exomes 𝑓: 0.92 (584630 hom.)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.43

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-31343172-C-G is Benign according to our data. Variant chr17-31343172-C-G is described in ClinVar as [Benign]. Clinvar id is 257300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3	c.7189+37C>G		intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.7126+37C>G		intron_variant			NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.7189+37C>G		intron_variant		1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134465 AN: 152130 Hom.: 59658 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.870

GnomAD3 exomes AF: 0.907 AC: 221128 AN: 243688 Hom.: 100531 AF XY: 0.912 AC XY: 120786 AN XY: 132478

Gnomad AFR exome AF: 0.799

Gnomad AMR exome AF: 0.887

Gnomad ASJ exome AF: 0.914

Gnomad EAS exome AF: 0.881

Gnomad SAS exome AF: 0.949

Gnomad FIN exome AF: 0.944

Gnomad NFE exome AF: 0.915

Gnomad OTH exome AF: 0.901

GnomAD4 exome AF: 0.916 AC: 1275297 AN: 1392570 Hom.: 584630 Cov.: 22 AF XY: 0.917 AC XY: 639141 AN XY: 696714

Gnomad4 AFR exome AF: 0.795

Gnomad4 AMR exome AF: 0.886

Gnomad4 ASJ exome AF: 0.918

Gnomad4 EAS exome AF: 0.925

Gnomad4 SAS exome AF: 0.949

Gnomad4 FIN exome AF: 0.945

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 0.901

GnomAD4 genome AF: 0.884 AC: 134554 AN: 152248 Hom.: 59692 Cov.: 32 AF XY: 0.888 AC XY: 66078 AN XY: 74450

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.919

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.950

Gnomad4 NFE AF: 0.918

Gnomad4 OTH AF: 0.867

Alfa AF: 0.902 Hom.: 11384

Bravo AF: 0.872

Asia WGS AF: 0.898 AC: 3120 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Neurofibromatosis, type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Neurofibromatosis, familial spinal Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.69

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: rs7405740; hg19: chr17-29670190;