chr12-25206244-G-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_004985.5(KRAS):c.*3551C>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 0.000245 in 212,336 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 0 hom. )
Consequence
KRAS
NM_004985.5 3_prime_UTR
NM_004985.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0880
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 12-25206244-G-C is Benign according to our data. Variant chr12-25206244-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 308071.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00023 (35/152200) while in subpopulation EAS AF= 0.00598 (31/5186). AF 95% confidence interval is 0.00433. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 36 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRAS | NM_004985.5 | c.*3551C>G | 3_prime_UTR_variant | 5/5 | ENST00000311936.8 | ||
KRAS | NM_033360.4 | c.*3672C>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.*3672C>G | 3_prime_UTR_variant | 6/6 | 1 | NM_033360.4 | A1 | ||
KRAS | ENST00000311936.8 | c.*3551C>G | 3_prime_UTR_variant | 5/5 | 1 | NM_004985.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152082Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
36
AN:
152082
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000283 AC: 17AN: 60136Hom.: 0 Cov.: 0 AF XY: 0.000214 AC XY: 6AN XY: 27996
GnomAD4 exome
AF:
AC:
17
AN:
60136
Hom.:
Cov.:
0
AF XY:
AC XY:
6
AN XY:
27996
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000230 AC: 35AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74424
GnomAD4 genome
?
AF:
AC:
35
AN:
152200
Hom.:
Cov.:
32
AF XY:
AC XY:
20
AN XY:
74424
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
11
AN:
3476
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Noonan syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | KRAS: BS1, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at