7-92234558-G-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2
The ENST00000394505.7(KRIT1):c.880C>A(p.Arg294=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,612,968 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
KRIT1
ENST00000394505.7 synonymous
ENST00000394505.7 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.35
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000131 (2/152166) while in subpopulation SAS AF= 0.000415 (2/4820). AF 95% confidence interval is 0.000073. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KRIT1 | NM_194454.3 | c.880C>A | p.Arg294= | synonymous_variant | 10/19 | ENST00000394505.7 | NP_919436.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KRIT1 | ENST00000394505.7 | c.880C>A | p.Arg294= | synonymous_variant | 10/19 | 1 | NM_194454.3 | ENSP00000378013 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152048Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251360Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135878
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460802Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726816
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74402
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at