17-31095237-G-C

Variant names:

• chr17-31095237-G-C
• rs886052795
• ENST00000579081.6:n.-73G>C

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.-73G>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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • 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: 0.992
• 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=-0.64).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.-73G>C		5_prime_UTR_variant	Exon 1 of 58	ENST00000358273.9	NP_001035957.1
MIR4733HG	NR_186435.1	n.254C>G		non_coding_transcript_exon_variant	Exon 1 of 4
NF1	NM_000267.4	c.-73G>C		5_prime_UTR_variant	Exon 1 of 57		NP_000258.1
NF1	NM_001128147.3	c.-73G>C		5_prime_UTR_variant	Exon 1 of 15		NP_001121619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.-73G>C		5_prime_UTR_variant	Exon 1 of 58	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00 AC: 0 AN: 130154 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1276612 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 634886

African (AFR) AF: 0.00 AC: 0 AN: 29628

American (AMR) AF: 0.00 AC: 0 AN: 35502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24484

East Asian (EAS) AF: 0.00 AC: 0 AN: 35172

South Asian (SAS) AF: 0.00 AC: 0 AN: 76956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3868

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 983332

Other (OTH) AF: 0.00 AC: 0 AN: 54136

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.93
PhyloP100		0.99
PromoterAI		-0.0072	Neutral

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: rs886052795; hg19: chr17-29422255;