chr1-114704709-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002524.5(NRAS):c.*3385G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 152,328 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0042 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NRAS
NM_002524.5 3_prime_UTR
NM_002524.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.31
Genes affected
NRAS (HGNC:7989): (NRAS proto-oncogene, GTPase) This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. This shuttling is regulated through palmitoylation and depalmitoylation by the ZDHHC9-GOLGA7 complex. The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. Mutations in this gene have been associated with somatic rectal cancer, follicular thyroid cancer, autoimmune lymphoproliferative syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia. [provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 1-114704709-C-T is Benign according to our data. Variant chr1-114704709-C-T is described in ClinVar as [Benign]. Clinvar id is 2639007.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00419 (638/152328) while in subpopulation AFR AF= 0.0143 (594/41570). AF 95% confidence interval is 0.0133. There are 2 homozygotes in gnomad4. There are 293 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 637 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRAS | NM_002524.5 | c.*3385G>A | 3_prime_UTR_variant | 7/7 | ENST00000369535.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRAS | ENST00000369535.5 | c.*3385G>A | 3_prime_UTR_variant | 7/7 | 1 | NM_002524.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00419 AC: 637AN: 152210Hom.: 2 Cov.: 33
GnomAD3 genomes
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33
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 4Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 4
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GnomAD4 genome ? AF: 0.00419 AC: 638AN: 152328Hom.: 2 Cov.: 33 AF XY: 0.00393 AC XY: 293AN XY: 74498
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?
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638
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152328
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33
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293
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | NRAS: BS1, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at