rs8080679

chr17-31275592-A-G

Variant summary

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

The NM_001042492.3(NF1):c.4835+10253A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,052 control chromosomes in the GnomAD database, including 25,505 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 0.54 (25505 hom., cov: 31)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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]

OMG (HGNC:8135): (oligodendrocyte myelin glycoprotein) Predicted to enable identical protein binding activity. Predicted to be involved in neuron projection regeneration. Predicted to act upstream of or within regulation of collateral sprouting of intact axon in response to injury. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3	c.4835+10253A>G		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.4772+10253A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.4835+10253A>G		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81889 AN: 151934 Hom.: 25512 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.539 AC: 81883 AN: 152052 Hom.: 25505 Cov.: 31 AF XY: 0.535 AC XY: 39732 AN XY: 74330

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.606

Alfa AF: 0.634 Hom.: 8158

Bravo AF: 0.518

Asia WGS AF: 0.519 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.0
Dann	Benign	0.21

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: rs8080679; hg19: chr17-29602610;