chr17-31095137-C-A

Variant names:

• chr17-31095137-C-A
• rs886052791
• NM_001042492.3:c.-173C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001042492.3(NF1):​c.-173C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 149,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000013 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00014 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: NF1 NM_001042492.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.-173C>A		5_prime_UTR_variant	Exon 1 of 58	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.-173C>A		5_prime_UTR_variant	Exon 1 of 57		NP_000258.1
NF1	NM_001128147.3	c.-173C>A		5_prime_UTR_variant	Exon 1 of 15		NP_001121619.1
MIR4733HG	NR_186435.1	n.264+90G>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273	c.-173C>A		5_prime_UTR_variant	Exon 1 of 58	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 149838 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000426

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000143 AC: 56 AN: 390854 Hom.: 1 Cov.: 3 AF XY: 0.000207 AC XY: 43 AN XY: 207842

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000408

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.0000378

Gnomad4 NFE exome AF: 0.0000172

Gnomad4 OTH exome AF: 0.0000439

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 149838 Hom.: 0 Cov.: 24 AF XY: 0.0000274 AC XY: 2 AN XY: 73116

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000426

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.87
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

Publications

LitVar

Other links and lift over

dbSNP: rs886052791; hg19: chr17-29422155;