rs752925099
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000256078.10(KRAS):c.*4+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000256078.10 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KRAS | NM_004985.5 | c.451-5518T>C | intron_variant | ENST00000311936.8 | NP_004976.2 | |||
KRAS | NM_033360.4 | c.*4+8T>C | splice_region_variant, intron_variant | ENST00000256078.10 | NP_203524.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRAS | ENST00000256078.10 | c.*4+8T>C | splice_region_variant, intron_variant | 1 | NM_033360.4 | ENSP00000256078 | A1 | |||
KRAS | ENST00000311936.8 | c.451-5518T>C | intron_variant | 1 | NM_004985.5 | ENSP00000308495 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251136Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135748
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1460974Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726816
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74382
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 14, 2017 | The *4+8T>C variant in KRAS has not been previously reported in affected individ uals. This variant has been identified in 5/111504 European chromosomes by the G enome Aggregation Database (gnomAD, http://gnomAD.broadinstitute.org; dbSNP rs75 2925099). Please note that for diseases with clinical variability, reduced penet rance, or recessive inheritance, pathogenic variants may be present at a low fre quency in the general population. Conservation analysis suggest that the *4+8T>C variant may not impact the protein, though this information is not predictive e nough to rule out pathogenicity. Please note, this variant occurs near an altern ative transcript. Functional studies provide some evidence that mice lacking thi s alternate transcript are viable, fertile, and show no histopathological abnorm alities (Plowman 2003). In summary, the clinical significance of the *4+8T>C va riant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at