chr17-31095259-C-T

Variant names:

• chr17-31095259-C-T
• rs964223360
• NM_001042492.3:c.-51C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001042492.3(NF1):​c.-51C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,366,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: NF1 NM_001042492.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:5
• Conservation: PhyloP100: 1.65
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BS2: High AC in GnomAdExome4 at 139 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042492.3. 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
	NF1	NM_001042492.3	MANE Select	c.-51C>T		5_prime_UTR	Exon 1 of 58	NP_001035957.1	P21359-1
	NF1	NM_000267.4		c.-51C>T		5_prime_UTR	Exon 1 of 57	NP_000258.1
	NF1	NM_001128147.3		c.-51C>T		5_prime_UTR	Exon 1 of 15	NP_001121619.1	P21359-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	ENST00000358273.9	TSL:1 MANE Select	c.-51C>T		5_prime_UTR	Exon 1 of 58	ENSP00000351015.4	P21359-1
	NF1	ENST00000356175.7	TSL:1	c.-51C>T		5_prime_UTR	Exon 1 of 57	ENSP00000348498.3	P21359-2
	NF1	ENST00000431387.8	TSL:1	c.-51C>T		5_prime_UTR	Exon 1 of 15	ENSP00000412921.4	P21359-5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.0000230 AC: 3 AN: 130314 AF XY: 0.0000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 139 AN: 1366416 Hom.: 0 Cov.: 30 AF XY: 0.0000933 AC XY: 63 AN XY: 675274

African (AFR) AF: 0.0000320 AC: 1 AN: 31228

American (AMR) AF: 0.0000281 AC: 1 AN: 35640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25052

East Asian (EAS) AF: 0.00 AC: 0 AN: 35662

South Asian (SAS) AF: 0.00 AC: 0 AN: 78744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4038

European-Non Finnish (NFE) AF: 0.000129 AC: 137 AN: 1064494

Other (OTH) AF: 0.00 AC: 0 AN: 57136

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Uncertain	0.99
PhyloP100		1.6
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2
Mutation Taster		=299/1	polymorphism

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

dbSNP: rs964223360; hg19: chr17-29422277;