rs2057769

chr17-31364350-C-A

Variant summary

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

The NM_001042492.3(NF1):c.8377+3647C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,086 control chromosomes in the GnomAD database, including 17,071 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 0.44 (17071 hom., cov: 32)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3	c.8377+3647C>A		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.8314+3647C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.8377+3647C>A		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66585 AN: 151966 Hom.: 17047 Cov.: 32

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.438 AC: 66660 AN: 152086 Hom.: 17071 Cov.: 32 AF XY: 0.443 AC XY: 32893 AN XY: 74314

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.378

Alfa AF: 0.390 Hom.: 2160

Bravo AF: 0.457

Asia WGS AF: 0.471 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.059
Dann	Benign	0.58

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: rs2057769; hg19: chr17-29691368;