17-31095058-G-GCC

Position:

• chr17-31095058-G-GCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001042492.3(NF1):​c.-248_-247dupCC 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 0.00010 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00015 (0 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: -0.297

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:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3	c.-248_-247dupCC		5_prime_UTR_variant	1/58	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.-248_-247dupCC		5_prime_UTR_variant	1/57		NP_000258.1
NF1	NM_001128147.3	c.-248_-247dupCC		5_prime_UTR_variant	1/15		NP_001121619.1
MIR4733HG	NR_186435.1	n.264+167_264+168dupGG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273	c.-248_-247dupCC		5_prime_UTR_variant	1/58	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 15 AN: 148626 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.0000745

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000487

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000449

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000146 AC: 60 AN: 410060 Hom.: 0 Cov.: 0 AF XY: 0.000163 AC XY: 35 AN XY: 214930

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000123

Gnomad4 ASJ exome AF: 0.000240

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000368

Gnomad4 FIN exome AF: 0.000138

Gnomad4 NFE exome AF: 0.000137

Gnomad4 OTH exome AF: 0.0000827

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000101 AC: 15 AN: 148726 Hom.: 0 Cov.: 31 AF XY: 0.0000552 AC XY: 4 AN XY: 72522

Gnomad4 AFR AF: 0.0000743

Gnomad4 AMR AF: 0.000269

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000487

Gnomad4 NFE AF: 0.0000449

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886052786; hg19: chr17-29422076;