chr17-31095259-C-A

Variant names:

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

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.-51C>A 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: 1.65
• 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=-0.66).

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>A		5_prime_UTR	Exon 1 of 58	NP_001035957.1	P21359-1
	NF1	NM_000267.4		c.-51C>A		5_prime_UTR	Exon 1 of 57	NP_000258.1
	NF1	NM_001128147.3		c.-51C>A		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>A		5_prime_UTR	Exon 1 of 58	ENSP00000351015.4	P21359-1
	NF1	ENST00000356175.7	TSL:1	c.-51C>A		5_prime_UTR	Exon 1 of 57	ENSP00000348498.3	P21359-2
	NF1	ENST00000431387.8	TSL:1	c.-51C>A		5_prime_UTR	Exon 1 of 15	ENSP00000412921.4	P21359-5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1366416 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 675272

African (AFR) AF: 0.00 AC: 0 AN: 31228

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 1064494

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

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.94
PhyloP100		1.6
PromoterAI		-0.024	Neutral
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;