Genetic Variant NM_001042492.3:c.-247dupC (chr17-31095058-G-GC) – ACMG Classification: Uncertain_significance (0 pts)

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.297

Publications

0 publications found

Variant links:

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]

NF1 links:

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

MIR4733HG links:

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ACMG classification

Classification was made for transcript

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 link	c.-247dupC		5_prime_UTR_variant	Exon 1 of 58	ENST00000358273.9	NP_001035957.1	P21359-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9 link	c.-247dupC		5_prime_UTR_variant	Exon 1 of 58	1	NM_001042492.3	ENSP00000351015.4		P21359-1

Frequencies

GnomAD3 genomes

AF:

0.000155

AC:

AN:

148580

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00145

AC XY:

311

AN XY:

214932

show subpopulations

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

African (AFR)

AF:

0.0000987

AC:

AN:

10132

American (AMR)

AF:

0.000615

AC:

AN:

16252

Ashkenazi Jewish (ASJ)

AF:

0.000720

AC:

AN:

12494

East Asian (EAS)

AF:

0.00

AC:

AN:

27496

South Asian (SAS)

AF:

0.00501

AC:

204

AN:

40736

European-Finnish (FIN)

AF:

0.00135

AC:

AN:

28980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1830

European-Non Finnish (NFE)

AF:

0.000835

AC:

207

AN:

247964

Other (OTH)

AF:

0.000620

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.363

Heterozygous variant carriers

117

146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000155

AC:

AN:

148680

Hom.:

Cov.:

AF XY:

0.000221

AC XY:

AN XY:

72488

show subpopulations

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

African (AFR)

AF:

0.000124

AC:

AN:

40382

American (AMR)

AF:

0.000539

AC:

AN:

14856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.00

AC:

AN:

5028

South Asian (SAS)

AF:

0.00

AC:

AN:

4710

European-Finnish (FIN)

AF:

0.000292

AC:

AN:

10260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000898

AC:

AN:

66782

Other (OTH)

AF:

0.000487

AC:

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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.271

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Publications

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NM_001042492.3:c.-247dupC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over