NM_001042492.3:c.-153C>T

Variant names:

• chr17-31095157-C-T
• rs2143141001
• NM_001042492.3:c.-153C>T

Variant summary

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

The NM_001042492.3(NF1):​c.-153C>T 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NF1 NM_001042492.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• 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=-0.57).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.-153C>T		5_prime_UTR_variant	Exon 1 of 58	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.4	c.-153C>T		5_prime_UTR_variant	Exon 1 of 57		NP_000258.1
NF1	NM_001128147.3	c.-153C>T		5_prime_UTR_variant	Exon 1 of 15		NP_001121619.1
MIR4733HG	NR_186435.1	n.264+70G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.-153C>T		5_prime_UTR_variant	Exon 1 of 58	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 509784 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 273274

African (AFR) AF: 0.00 AC: 0 AN: 12754

American (AMR) AF: 0.00 AC: 0 AN: 29834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17934

East Asian (EAS) AF: 0.00 AC: 0 AN: 28004

South Asian (SAS) AF: 0.00 AC: 0 AN: 59272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 299578

Other (OTH) AF: 0.00 AC: 0 AN: 28338

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.90
PhyloP100		0.024
PromoterAI		-0.076	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs2143141001; hg19: chr17-29422175;