17-31095064-T-TC

Position:

• chr17-31095064-T-TC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001042492.3(NF1):​c.-242dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 29)
  • Exomes 𝑓: 0.014 (8 hom.)
  • Failed GnomAD Quality Control
• Consequence: NF1 NM_001042492.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:4
• Conservation: PhyloP100: 0.545

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]

MIR4733HG (HGNC:55332): (MIR4733 host gene)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3	c.-242dup		5_prime_UTR_variant	1/58	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.-242dup		5_prime_UTR_variant	1/57		NP_000258.1
NF1	NM_001128147.3	c.-242dup		5_prime_UTR_variant	1/15		NP_001121619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.-242dup		5_prime_UTR_variant	1/58	1	NM_001042492.3	ENSP00000351015	P1
MIR4733HG	ENST00000583377.1	n.224+162_224+163insG		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 59 AN: 93988 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.000588

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00126

Gnomad ASJ AF: 0.000430

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000672

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000466

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0144 AC: 3479 AN: 240768 Hom.: 8 Cov.: 0 AF XY: 0.0172 AC XY: 2149 AN XY: 124764

Gnomad4 AFR exome AF: 0.00173

Gnomad4 AMR exome AF: 0.00999

Gnomad4 ASJ exome AF: 0.00859

Gnomad4 EAS exome AF: 0.000251

Gnomad4 SAS exome AF: 0.0846

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.00856

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000628 AC: 59 AN: 93992 Hom.: 0 Cov.: 29 AF XY: 0.000659 AC XY: 30 AN XY: 45538

Gnomad4 AFR AF: 0.000587

Gnomad4 AMR AF: 0.00126

Gnomad4 ASJ AF: 0.000430

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000676

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.000466

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:4

Revision: criteria provided, single submitter

Submissions by phenotype

Neurofibromatosis, type 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Neurofibromatosis, familial spinal Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Neurofibromatosis-Noonan syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Café-au-lait macules with pulmonary stenosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs886052787; hg19: chr17-29422082;