rs200000378
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_194454.3(KRIT1):c.486-37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,606,376 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 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
KRIT1
NM_194454.3 intron
NM_194454.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.130
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000105 (16/152156) while in subpopulation AFR AF= 0.00029 (12/41430). AF 95% confidence interval is 0.000167. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRIT1 | NM_194454.3 | c.486-37C>T | intron_variant | ENST00000394505.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRIT1 | ENST00000394505.7 | c.486-37C>T | intron_variant | 1 | NM_194454.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152156Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000768 AC: 19AN: 247548Hom.: 0 AF XY: 0.0000670 AC XY: 9AN XY: 134274
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GnomAD4 exome AF: 0.0000997 AC: 145AN: 1454220Hom.: 0 Cov.: 29 AF XY: 0.000109 AC XY: 79AN XY: 723812
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74338
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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