ENST00000579081.6:n.-8G>C

Variant names:

• chr17-31095200-A-C
• NM_001042492.3:c.-110A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000579081.6(NF1):​n.-110A>C variant causes a upstream gene 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: NF1 ENST00000579081.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000579081.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	NM_001042492.3	MANE Select	c.-110A>C		5_prime_UTR	Exon 1 of 58	NP_001035957.1
	NF1	NM_000267.4		c.-110A>C		5_prime_UTR	Exon 1 of 57	NP_000258.1
	NF1	NM_001128147.3		c.-110A>C		5_prime_UTR	Exon 1 of 15	NP_001121619.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	ENST00000358273.9	TSL:1 MANE Select	c.-110A>C		5_prime_UTR	Exon 1 of 58	ENSP00000351015.4
	NF1	ENST00000356175.7	TSL:1	c.-110A>C		5_prime_UTR	Exon 1 of 57	ENSP00000348498.3
	NF1	ENST00000431387.8	TSL:1	c.-110A>C		5_prime_UTR	Exon 1 of 15	ENSP00000412921.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		1.6
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr17-29422218;