7-92199351-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_004912.4(KRIT1):​c.*1385A>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 0.1 in 152,262 control chromosomes in the GnomAD database, including 981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 981 hom., cov: 32)
Failed GnomAD Quality Control

Consequence

KRIT1
NM_004912.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.544
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 Benign. Variant got -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 7-92199351-T-C is Benign according to our data. Variant chr7-92199351-T-C is described in ClinVar as [Benign]. Clinvar id is 360865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KRIT1NM_001013406.2 linkuse as main transcriptc.*1385A>G 3_prime_UTR_variant 17/17 NP_001013424.1
KRIT1NM_001350669.1 linkuse as main transcriptc.*1385A>G 3_prime_UTR_variant 17/17 NP_001337598.1
KRIT1NM_001350670.1 linkuse as main transcriptc.*1385A>G 3_prime_UTR_variant 18/18 NP_001337599.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KRIT1ENST00000394507.5 linkuse as main transcriptc.*1385A>G 3_prime_UTR_variant 20/205 ENSP00000378015 P1O00522-1
KRIT1ENST00000692807.1 linkuse as main transcriptc.*1385A>G 3_prime_UTR_variant 17/17 ENSP00000508564 P1O00522-1
KRIT1ENST00000688180.1 linkuse as main transcriptn.2648A>G non_coding_transcript_exon_variant 7/7

Frequencies

GnomAD3 genomes
AF:
0.100
AC:
15226
AN:
152144
Hom.:
981
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0263
Gnomad AMI
AF:
0.293
Gnomad AMR
AF:
0.0806
Gnomad ASJ
AF:
0.109
Gnomad EAS
AF:
0.0266
Gnomad SAS
AF:
0.104
Gnomad FIN
AF:
0.155
Gnomad MID
AF:
0.225
Gnomad NFE
AF:
0.143
Gnomad OTH
AF:
0.101
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AC:
0
AN:
0
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
GnomAD4 genome
AF:
0.100
AC:
15221
AN:
152262
Hom.:
981
Cov.:
32
AF XY:
0.0994
AC XY:
7398
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0261
Gnomad4 AMR
AF:
0.0804
Gnomad4 ASJ
AF:
0.109
Gnomad4 EAS
AF:
0.0266
Gnomad4 SAS
AF:
0.104
Gnomad4 FIN
AF:
0.155
Gnomad4 NFE
AF:
0.143
Gnomad4 OTH
AF:
0.102
Alfa
AF:
0.127
Hom.:
271
Bravo
AF:
0.0899
Asia WGS
AF:
0.0910
AC:
316
AN:
3470

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Angiokeratoma corporis diffusum with arteriovenous fistulas Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Cerebral cavernous malformation Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
CADD
Benign
11
DANN
Benign
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs62467792; hg19: chr7-91828665; API