chr12-25209872-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PVS1_StrongPM2BP6_Moderate
The NM_004985.5(KRAS):c.490C>T(p.Arg164Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,806 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
KRAS
NM_004985.5 stop_gained
NM_004985.5 stop_gained
Scores
1
4
2
Clinical Significance
Conservation
PhyloP100: 7.50
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 Uncertain_significance. Variant got 4 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.136 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 12-25209872-G-A is Benign according to our data. Variant chr12-25209872-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 547512.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRAS | NM_004985.5 | c.490C>T | p.Arg164Ter | stop_gained | 5/5 | ENST00000311936.8 | |
KRAS | NM_033360.4 | c.*44C>T | 3_prime_UTR_variant | 6/6 | ENST00000256078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRAS | ENST00000311936.8 | c.490C>T | p.Arg164Ter | stop_gained | 5/5 | 1 | NM_004985.5 | P4 | |
KRAS | ENST00000256078.10 | c.*44C>T | 3_prime_UTR_variant | 6/6 | 1 | NM_033360.4 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1456806Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 724866
GnomAD4 exome
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30
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1
AN XY:
724866
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Noonan syndrome 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D;D;D
Vest4
GERP RS
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