17-31232069-T-TTTC

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP6_ModerateBS2_Supporting

The ENST00000358273.9(NF1):​c.3198-4_3198-3insTTC variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

NF1
ENST00000358273.9 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.140
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP6
Variant 17-31232069-T-TTTC is Benign according to our data. Variant chr17-31232069-T-TTTC is described in ClinVar as [Likely_benign]. Clinvar id is 457631.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 7 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/exons MANE Protein UniProt
NF1NM_001042492.3 linkuse as main transcriptc.3198-4_3198-3insTTC splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000358273.9 NP_001035957.1
NF1NM_000267.3 linkuse as main transcriptc.3198-4_3198-3insTTC splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant NP_000258.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NF1ENST00000358273.9 linkuse as main transcriptc.3198-4_3198-3insTTC splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_001042492.3 ENSP00000351015 P1P21359-1

Frequencies

GnomAD3 genomes
AF:
0.0000479
AC:
7
AN:
145986
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0000528
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:
0.0000745
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000344
AC:
4
AN:
1161256
Hom.:
0
Cov.:
3
AF XY:
0.00000172
AC XY:
1
AN XY:
581726
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000330
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000341
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000479
AC:
7
AN:
145986
Hom.:
0
Cov.:
0
AF XY:
0.0000702
AC XY:
5
AN XY:
71198
show subpopulations
Gnomad4 AFR
AF:
0.0000528
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000745
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Neurofibromatosis, type 1 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 18, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs864622717; hg19: chr17-29559087; API