rs7226006

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000358273.9(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 ENST00000358273.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NF1	NM_001042492.3	c.4836-2182A>G		intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.4773-2182A>G		intron_variant			NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.4836-2182A>G		intron_variant		1	NM_001042492.3	ENSP00000351015	P1

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

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.327

Alfa AF: 0.325 Hom.: 3941

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7226006; hg19: chr17-29650656;