GeneBe

7-92222966-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.85
Variant links:
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRIT1NM_194454.3 linkc.1267C>A p.Arg423Arg synonymous_variant Exon 13 of 19 ENST00000394505.7 NP_919436.1 O00522-1A4D1F7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRIT1ENST00000394505.7 linkc.1267C>A p.Arg423Arg synonymous_variant Exon 13 of 19 1 NM_194454.3 ENSP00000378013.2 O00522-1
ENSG00000289027ENST00000692281.1 linkc.1267C>A p.Arg423Arg synonymous_variant Exon 13 of 26 ENSP00000510568.1 A0A8I5KWQ7
ENSG00000285953ENST00000458493.6 linkc.1267C>A p.Arg423Arg synonymous_variant Exon 12 of 20 4 ENSP00000396352.2 C9JD81

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455548
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
724516
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
CADD
Benign
4.3
DANN
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.35
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.35
Position offset: 12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-91852280; API