rs17881467

Variant names:

• chr17-31229969-G-A
• rs17881467
• NM_001042492.3:c.2985G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-31229969-G-A
• chr17-31229969-G-C
• chr17-31229969-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001042492.3(NF1):​c.2985G>A​(p.Leu995Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L995L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NF1 NM_001042492.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.396

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 17-31229969-G-A is Benign according to our data. Variant chr17-31229969-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1465095.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.396 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.2985G>A	p.Leu995Leu	synonymous_variant	Exon 22 of 58	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.2985G>A	p.Leu995Leu	synonymous_variant	Exon 22 of 57		NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.2985G>A	p.Leu995Leu	synonymous_variant	Exon 22 of 58	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459464 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726046

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33396

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44714

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26120

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39678

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86158

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53410

Gnomad4 NFE exome AF: 9.00e-7 AC: 1 AN: 1111664

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60188

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurofibromatosis, type 1 Benign:1

Feb 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	5.1
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs17881467; hg19: chr17-29556987;