7-92200357-A-AT

Variant names:

• chr7-92200357-A-AT
• rs34910226
• ENST00000412043.6:c.*378dupA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000412043.6(KRIT1):​c.*378dupA variant causes a splice region change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (9836 hom., cov: 0)
  • Exomes 𝑓: 0.26 (469 hom.)
• Consequence: KRIT1 ENST00000412043.6 splice_region
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.283

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]

ENSG00000289027 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-92200357-A-AT is Benign according to our data. Variant chr7-92200357-A-AT is described in ClinVar as [Benign]. Clinvar id is 360872.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRIT1	NM_194454.3	c.*378dupA		3_prime_UTR_variant	Exon 19 of 19	ENST00000394505.7	NP_919436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRIT1	ENST00000394505	c.*378dupA		3_prime_UTR_variant	Exon 19 of 19	1	NM_194454.3	ENSP00000378013.2
ENSG00000289027	ENST00000692281.1	c.2025+12837dupA		intron_variant	Intron 17 of 25			ENSP00000510568.1
ENSG00000285953	ENST00000458493.6	c.2025+12837dupA		intron_variant	Intron 16 of 19	4		ENSP00000396352.2

Frequencies

GnomAD3 genomes AF: 0.367 AC: 53036 AN: 144686 Hom.: 9842 Cov.: 0

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.391

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.256 AC: 19099 AN: 74712 Hom.: 469 Cov.: 0 AF XY: 0.253 AC XY: 9926 AN XY: 39302

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.366 AC: 53037 AN: 144714 Hom.: 9836 Cov.: 0 AF XY: 0.363 AC XY: 25387 AN XY: 70018

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.391

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Angiokeratoma corporis diffusum with arteriovenous fistulas Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cerebral cavernous malformation Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34910226; hg19: chr7-91829671;