17-31168877-T-G

Position:

• chr17-31168877-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.480-1014T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,158 control chromosomes in the GnomAD database, including 3,721 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 0.20 (3721 hom., cov: 31)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3	c.480-1014T>G		intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.480-1014T>G		intron_variant			NP_000258.1
NF1	NM_001128147.3	c.480-1014T>G		intron_variant			NP_001121619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.480-1014T>G		intron_variant		1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30269 AN: 152040 Hom.: 3724 Cov.: 31

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.199 AC: 30252 AN: 152158 Hom.: 3721 Cov.: 31 AF XY: 0.200 AC XY: 14870 AN XY: 74396

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.208

Alfa AF: 0.254 Hom.: 3174

Bravo AF: 0.189

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.77

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: rs2953014; hg19: chr17-29495895;