17-31095064-T-TC

Variant names:

• chr17-31095064-T-TC
• rs886052787
• NM_001042492.3:c.-242dupC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001042492.3(NF1):​c.-242dupC 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.-242dupC		5_prime_UTR_variant	Exon 1 of 58	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.4	c.-242dupC		5_prime_UTR_variant	Exon 1 of 57		NP_000258.1
NF1	NM_001128147.3	c.-242dupC		5_prime_UTR_variant	Exon 1 of 15		NP_001121619.1
MIR4733HG	NR_186435.1	n.264+162dupG		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.-242dupC		5_prime_UTR_variant	Exon 1 of 58	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.000628 AC: 59 AN: 93988 Hom.: 0 Cov.: 29

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

African (AFR) AF: 0.00173 AC: 11 AN: 6366

American (AMR) AF: 0.00999 AC: 80 AN: 8006

Ashkenazi Jewish (ASJ) AF: 0.00859 AC: 67 AN: 7796

East Asian (EAS) AF: 0.000251 AC: 5 AN: 19896

South Asian (SAS) AF: 0.0846 AC: 1168 AN: 13800

European-Finnish (FIN) AF: 0.0102 AC: 186 AN: 18292

Middle Eastern (MID) AF: 0.00911 AC: 10 AN: 1098

European-Non Finnish (NFE) AF: 0.0121 AC: 1825 AN: 150678

Other (OTH) AF: 0.00856 AC: 127 AN: 14836

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000587 AC: 14 AN: 23868

American (AMR) AF: 0.00126 AC: 11 AN: 8760

Ashkenazi Jewish (ASJ) AF: 0.000430 AC: 1 AN: 2328

East Asian (EAS) AF: 0.00 AC: 0 AN: 3682

South Asian (SAS) AF: 0.000676 AC: 2 AN: 2958

European-Finnish (FIN) AF: 0.00189 AC: 10 AN: 5280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 188

European-Non Finnish (NFE) AF: 0.000466 AC: 21 AN: 45092

Other (OTH) AF: 0.00 AC: 0 AN: 1238

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:4

Revision: criteria provided, single submitter

Submissions by phenotype

Neurofibromatosis, type 1 Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Neurofibromatosis, familial spinal Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Neurofibromatosis-Noonan syndrome Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.55

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

Other links and lift over

dbSNP: rs886052787; hg19: chr17-29422082;