rs7226006

Variant names:

• chr17-31323638-A-G
• rs7226006
• NM_001042492.3:c.4836-2182A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-31323638-A-G
• chr17-31323638-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042492.3(NF1):​c.4836-2182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,956 control chromosomes in the GnomAD database, including 10,897 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (10897 hom., cov: 31)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.4836-2182A>G		intron_variant	Intron 36 of 57	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.4	c.4773-2182A>G		intron_variant	Intron 35 of 56		NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.4836-2182A>G		intron_variant	Intron 36 of 57	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55954 AN: 151838 Hom.: 10877 Cov.: 31

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.327

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.369 AC: 56006 AN: 151956 Hom.: 10897 Cov.: 31 AF XY: 0.375 AC XY: 27869 AN XY: 74256

African (AFR) AF: 0.466 AC: 19315 AN: 41438

American (AMR) AF: 0.426 AC: 6511 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2742 AN: 5160

South Asian (SAS) AF: 0.383 AC: 1848 AN: 4820

European-Finnish (FIN) AF: 0.345 AC: 3637 AN: 10536

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20140 AN: 67944

Other (OTH) AF: 0.327 AC: 691 AN: 2112

Alfa AF: 0.333 Hom.: 6098

Bravo AF: 0.377

Asia WGS AF: 0.452 AC: 1571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.9
DANN	Benign	0.83
PhyloP100		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7226006; hg19: chr17-29650656;