rs1911498673

Variant names:

• chr17-31094947-T-C
• rs1911498673
• ENST00000356175.7:c.-363T>C

Variant summary

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

The ENST00000356175.7(NF1):​c.-363T>C variant causes a 5 prime UTR 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NF1 ENST00000356175.7 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:4
• Conservation: PhyloP100: 1.81
• 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=-0.53).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000356175.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR4733HG	NR_186435.1		n.264+280A>G		intron	N/A
	NF1	NM_001042492.3	MANE Select	c.-363T>C		upstream_gene	N/A	NP_001035957.1	P21359-1
	NF1	NM_000267.4		c.-363T>C		upstream_gene	N/A	NP_000258.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	ENST00000356175.7	TSL:1	c.-363T>C		5_prime_UTR	Exon 1 of 57	ENSP00000348498.3	P21359-2
	NF1	ENST00000487476.5	TSL:1	c.-363T>C		5_prime_UTR	Exon 1 of 14	ENSP00000491589.1	P21359-3
	NF1	ENST00000696138.1		c.-363T>C		5_prime_UTR	Exon 1 of 59	ENSP00000512431.1	A0A8Q3WL04

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 351356 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 184058

African (AFR) AF: 0.00 AC: 0 AN: 8164

American (AMR) AF: 0.00 AC: 0 AN: 11690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11310

East Asian (EAS) AF: 0.00 AC: 0 AN: 24614

South Asian (SAS) AF: 0.00 AC: 0 AN: 29430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1648

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 216580

Other (OTH) AF: 0.00 AC: 0 AN: 21290

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Café-au-lait macules with pulmonary stenosis (1)
-	1	-	Neurofibromatosis-Noonan syndrome (1)
-	1	-	Neurofibromatosis, familial spinal (1)
-	1	-	Neurofibromatosis, type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.91
PhyloP100		1.8
PromoterAI		-0.38	Neutral

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: rs1911498673; hg19: chr17-29421965;