17-31095137-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_001042492.3(NF1):​c.-173C>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 0.0000111 in 540,692 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 0.0000067 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: NF1 NM_001042492.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BS2: High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.-173C>T		5_prime_UTR_variant	Exon 1 of 58	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.4	c.-173C>T		5_prime_UTR_variant	Exon 1 of 57		NP_000258.1
NF1	NM_001128147.3	c.-173C>T		5_prime_UTR_variant	Exon 1 of 15		NP_001121619.1
MIR4733HG	NR_186435.1	n.264+90G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.-173C>T		5_prime_UTR_variant	Exon 1 of 58	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.00000667 AC: 1 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000128 AC: 5 AN: 390854 Hom.: 0 Cov.: 3 AF XY: 0.00000481 AC XY: 1 AN XY: 207842

African (AFR) AF: 0.00 AC: 0 AN: 9478

American (AMR) AF: 0.00 AC: 0 AN: 17380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13260

East Asian (EAS) AF: 0.000163 AC: 4 AN: 24490

South Asian (SAS) AF: 0.00 AC: 0 AN: 42662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1772

European-Non Finnish (NFE) AF: 0.00000430 AC: 1 AN: 232568

Other (OTH) AF: 0.00 AC: 0 AN: 22778

GnomAD4 genome AF: 0.00000667 AC: 1 AN: 149838 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 73116

African (AFR) AF: 0.00 AC: 0 AN: 40762

American (AMR) AF: 0.00 AC: 0 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3434

East Asian (EAS) AF: 0.00 AC: 0 AN: 5006

South Asian (SAS) AF: 0.00 AC: 0 AN: 4692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67260

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		0.23
PromoterAI		-0.019	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: rs886052791; hg19: chr17-29422155;