rs727505314
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_033360.4(KRAS):c.451-3C>T variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000541 in 1,607,920 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 (★★).
Frequency
Consequence
NM_033360.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KRAS | NM_004985.5 | c.451-5652C>T | intron_variant | Intron 4 of 4 | ENST00000311936.8 | NP_004976.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151908Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251076Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135748
GnomAD4 exome AF: 0.0000556 AC: 81AN: 1456012Hom.: 0 Cov.: 29 AF XY: 0.0000497 AC XY: 36AN XY: 724708
GnomAD4 genome AF: 0.0000395 AC: 6AN: 151908Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74174
ClinVar
Submissions by phenotype
not specified Benign:1
c.451-3C>T in intron 4 of KRAS: This variant is not expected to have clinical s ignificance because it is located in an alternate transcript (KRAS-A) that is no t predicted to be essential for development and was identified by our laboratory in an unaffected parent of an individual with clinical features of Noonan syndr ome. Functional studies provide some evidence that mice lacking this alternate t ranscript were viable, fertile, and showed no histopathological abnormalities (P lowman 2003). It is located in the 3' splice region of KRAS-A, but computational tools do not suggest an impact to splicing. Additionally, no pathogenic sequenc e variants in this region of the KRAS gene have been identified in individuals w ith RASopathies to date. -
Malignant tumor of urinary bladder;C0023467:Acute myeloid leukemia;C0024623:Gastric cancer;C0235974:Carcinoma of pancreas;C0242379:Lung cancer;C0346153:Familial cancer of breast;C0917804:Cerebral arteriovenous malformation;C1838329:Toriello-Lacassie-Droste syndrome;C1860991:Noonan syndrome 3;C2674723:Autoimmune lymphoproliferative syndrome type 4;C3809005:Cardiofaciocutaneous syndrome 2;C4552097:Linear nevus sebaceous syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at