rs61764370
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004985.5(KRAS):c.*2505T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 195,932 control chromosomes in the GnomAD database, including 528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.062 ( 390 hom., cov: 31)
Exomes 𝑓: 0.073 ( 138 hom. )
Consequence
KRAS
NM_004985.5 3_prime_UTR
NM_004985.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.836
Genes affected
KRAS (HGNC:6407): (KRAS proto-oncogene, GTPase) This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 12-25207290-A-C is Benign according to our data. Variant chr12-25207290-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 308084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-25207290-A-C is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRAS | NM_004985.5 | c.*2505T>G | 3_prime_UTR_variant | 5/5 | ENST00000311936.8 | ||
KRAS | NM_033360.4 | c.*2626T>G | 3_prime_UTR_variant | 6/6 | ENST00000256078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRAS | ENST00000256078.10 | c.*2626T>G | 3_prime_UTR_variant | 6/6 | 1 | NM_033360.4 | A1 | ||
KRAS | ENST00000311936.8 | c.*2505T>G | 3_prime_UTR_variant | 5/5 | 1 | NM_004985.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0617 AC: 9391AN: 152092Hom.: 389 Cov.: 31
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GnomAD4 exome AF: 0.0726 AC: 3176AN: 43722Hom.: 138 Cov.: 0 AF XY: 0.0744 AC XY: 1516AN XY: 20390
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GnomAD4 genome ? AF: 0.0617 AC: 9396AN: 152210Hom.: 390 Cov.: 31 AF XY: 0.0588 AC XY: 4375AN XY: 74424
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Noonan syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
RASopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Noonan syndrome and Noonan-related syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 01, 2017 | - - |
Computational scores
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at