rs2525565

Positions:

• chr17-31339570-T-C
• chr17-31339570-T-G

Variant summary

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

The NM_001042492.3(NF1):​c.6921+765T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,996 control chromosomes in the GnomAD database, including 21,229 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 0.51 (21229 hom., cov: 31)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3	c.6921+765T>C		intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.6858+765T>C		intron_variant			NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.6921+765T>C		intron_variant		1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77267 AN: 151878 Hom.: 21220 Cov.: 31

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.509 AC: 77302 AN: 151996 Hom.: 21229 Cov.: 31 AF XY: 0.505 AC XY: 37556 AN XY: 74302

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.537

Alfa AF: 0.572 Hom.: 5245

Bravo AF: 0.487

Asia WGS AF: 0.443 AC: 1538 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.86

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: rs2525565; hg19: chr17-29666588;