rs2057769

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001042492.3(NF1):​c.8377+3647C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,086 control chromosomes in the GnomAD database, including 17,071 homozygotes. 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 0.44 ( 17071 hom., cov: 32)

Consequence

NF1
NM_001042492.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.56
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NF1NM_001042492.3 linkuse as main transcriptc.8377+3647C>A intron_variant ENST00000358273.9
NF1NM_000267.3 linkuse as main transcriptc.8314+3647C>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NF1ENST00000358273.9 linkuse as main transcriptc.8377+3647C>A intron_variant 1 NM_001042492.3 P1P21359-1

Frequencies

GnomAD3 genomes
AF:
0.438
AC:
66585
AN:
151966
Hom.:
17047
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.706
Gnomad AMI
AF:
0.280
Gnomad AMR
AF:
0.453
Gnomad ASJ
AF:
0.237
Gnomad EAS
AF:
0.533
Gnomad SAS
AF:
0.384
Gnomad FIN
AF:
0.345
Gnomad MID
AF:
0.225
Gnomad NFE
AF:
0.298
Gnomad OTH
AF:
0.378
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.438
AC:
66660
AN:
152086
Hom.:
17071
Cov.:
32
AF XY:
0.443
AC XY:
32893
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.705
Gnomad4 AMR
AF:
0.453
Gnomad4 ASJ
AF:
0.237
Gnomad4 EAS
AF:
0.533
Gnomad4 SAS
AF:
0.385
Gnomad4 FIN
AF:
0.345
Gnomad4 NFE
AF:
0.298
Gnomad4 OTH
AF:
0.378
Alfa
AF:
0.390
Hom.:
2160
Bravo
AF:
0.457
Asia WGS
AF:
0.471
AC:
1637
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.059
DANN
Benign
0.58

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

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

Other links and lift over

dbSNP: rs2057769; hg19: chr17-29691368; API