chr17-31095058-G-GC

Variant names:

• chr17-31095058-G-GC
• rs886052786
• NM_001042492.3:c.-247dupC

Variant summary

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

The NM_001042492.3(NF1):​c.-247dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NF1 NM_001042492.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• 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.-247dupC		5_prime_UTR_variant	Exon 1 of 58	ENST00000358273.9	NP_001035957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.-247dupC		5_prime_UTR_variant	Exon 1 of 58	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.000155 AC: 23 AN: 148580 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000539

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000292

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000898

Gnomad OTH AF: 0.000492

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00118 AC: 485 AN: 410074 Hom.: 0 Cov.: 0 AF XY: 0.00145 AC XY: 311 AN XY: 214932

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

African (AFR) AF: 0.0000987 AC: 1 AN: 10132

American (AMR) AF: 0.000615 AC: 10 AN: 16252

Ashkenazi Jewish (ASJ) AF: 0.000720 AC: 9 AN: 12494

East Asian (EAS) AF: 0.00 AC: 0 AN: 27496

South Asian (SAS) AF: 0.00501 AC: 204 AN: 40736

European-Finnish (FIN) AF: 0.00135 AC: 39 AN: 28980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1830

European-Non Finnish (NFE) AF: 0.000835 AC: 207 AN: 247964

Other (OTH) AF: 0.000620 AC: 15 AN: 24190

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000155 AC: 23 AN: 148680 Hom.: 0 Cov.: 31 AF XY: 0.000221 AC XY: 16 AN XY: 72488

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

African (AFR) AF: 0.000124 AC: 5 AN: 40382

American (AMR) AF: 0.000539 AC: 8 AN: 14856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5028

South Asian (SAS) AF: 0.00 AC: 0 AN: 4710

European-Finnish (FIN) AF: 0.000292 AC: 3 AN: 10260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000898 AC: 6 AN: 66782

Other (OTH) AF: 0.000487 AC: 1 AN: 2054

⚠️ 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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.30

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: rs886052786; hg19: chr17-29422076;