chr7-92222966-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_194454.3(KRIT1):c.1267C>A(p.Arg423Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000687 in 1,455,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
KRIT1
NM_194454.3 synonymous
NM_194454.3 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.85
Publications
0 publications found
Genes affected
KRIT1 (HGNC:1573): (KRIT1 ankyrin repeat containing) This gene encodes a protein containing four ankyrin repeats, a band 4.1/ezrin/radixin/moesin (FERM) domain, and multiple NPXY sequences. The encoded protein is localized in the nucleus and cytoplasm. It binds to integrin cytoplasmic domain-associated protein-1 alpha (ICAP1alpha), and plays a critical role in beta1-integrin-mediated cell proliferation. It associates with junction proteins and RAS-related protein 1A (Rap1A), which requires the encoded protein for maintaining the integrity of endothelial junctions. It is also a microtubule-associated protein and may play a role in microtubule targeting. Mutations in this gene result in cerebral cavernous malformations. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]
KRIT1 Gene-Disease associations (from GenCC):
- cerebral cavernous malformation 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- famililal cerebral cavernous malformationsInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRIT1 | ENST00000394505.7 | c.1267C>A | p.Arg423Arg | synonymous_variant | Exon 13 of 19 | 1 | NM_194454.3 | ENSP00000378013.2 | ||
ENSG00000289027 | ENST00000692281.1 | c.1267C>A | p.Arg423Arg | synonymous_variant | Exon 13 of 26 | ENSP00000510568.1 | ||||
ENSG00000285953 | ENST00000458493.6 | c.1267C>A | p.Arg423Arg | synonymous_variant | Exon 12 of 20 | 4 | ENSP00000396352.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455548Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 724516 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1455548
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
724516
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33348
American (AMR)
AF:
AC:
0
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26092
East Asian (EAS)
AF:
AC:
1
AN:
39622
South Asian (SAS)
AF:
AC:
0
AN:
86134
European-Finnish (FIN)
AF:
AC:
0
AN:
52826
Middle Eastern (MID)
AF:
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1106876
Other (OTH)
AF:
AC:
0
AN:
60182
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 12
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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