chr17-31095037-A-T

Variant names:

• chr17-31095037-A-T
• rs2143139374
• NM_001042492.3:c.-273A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042492.3(NF1):​c.-273A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NF1 NM_001042492.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.-273A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 58	ENST00000358273.9	NP_001035957.1
NF1	NM_001042492.3	c.-273A>T		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.-273A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 58	1	NM_001042492.3	ENSP00000351015.4
NF1	ENST00000358273.9	c.-273A>T		5_prime_UTR_variant	Exon 1 of 58	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 431906 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 227406

African (AFR) AF: 0.00 AC: 0 AN: 10596

American (AMR) AF: 0.00 AC: 0 AN: 17842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13084

East Asian (EAS) AF: 0.00 AC: 0 AN: 28646

South Asian (SAS) AF: 0.00 AC: 0 AN: 45526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1908

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 259318

Other (OTH) AF: 0.00 AC: 0 AN: 25194

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurofibromatosis, type 1 Uncertain:1

Dec 16, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant occurs in a non-coding region of the NF1 gene. It does not change the encoded amino acid sequence of the NF1 protein. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.93
PhyloP100		3.1
PromoterAI		-0.0072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2143139374; hg19: chr17-29422055;