chr7-92245996-C-T

Position:

chr7-92245996-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019004.2(ANKIB1):c.-614C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 234,902 control chromosomes in the GnomAD database, including 1,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 779 hom., cov: 31)

Exomes 𝑓: 0.097 ( 530 hom. )

Consequence

ANKIB1
NM_019004.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0480

Variant links:

Genes affected

ANKIB1 (HGNC:22215): (ankyrin repeat and IBR domain containing 1) Predicted to enable ubiquitin conjugating enzyme binding activity and ubiquitin protein ligase activity. Predicted to be involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process; protein polyubiquitination; and ubiquitin-dependent protein catabolic process. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANKIB1 links:

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]

KRIT1 links:

KRIT1 (HGNC:):

KRIT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 7-92245996-C-T is Benign according to our data. Variant chr7-92245996-C-T is described in ClinVar as [Benign]. Clinvar id is 360905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKIB1	NM_019004.2 linkuse as main transcript	c.-614C>T		5_prime_UTR_premature_start_codon_gain_variant	1/20	ENST00000265742.8	NP_061877.1	Q9P2G1
ANKIB1	NM_019004.2 linkuse as main transcript	c.-614C>T		5_prime_UTR_variant	1/20	ENST00000265742.8	NP_061877.1	Q9P2G1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKIB1	ENST00000265742 linkuse as main transcript	c.-614C>T		5_prime_UTR_premature_start_codon_gain_variant	1/20	1	NM_019004.2	ENSP00000265742.3		Q9P2G1
ANKIB1	ENST00000265742 linkuse as main transcript	c.-614C>T		5_prime_UTR_variant	1/20	1	NM_019004.2	ENSP00000265742.3		Q9P2G1

Frequencies

GnomAD3 genomes

AF:

0.0857

AC:

13037

AN:

152086

Hom.:

778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0571

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0819

Gnomad ASJ

AF:

0.0847

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.0792

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0781

Gnomad OTH

AF:

0.0930

GnomAD4 exome

AF:

0.0967

AC:

7997

AN:

82698

Hom.:

530

Cov.:

AF XY:

0.105

AC XY:

4766

AN XY:

45508

show subpopulations

Gnomad4 AFR exome

AF:

0.0718

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.0710

Gnomad4 EAS exome

AF:

0.430

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.0794

Gnomad4 NFE exome

AF:

0.0803

Gnomad4 OTH exome

AF:

0.0859

GnomAD4 genome

AF:

0.0857

AC:

13043

AN:

152204

Hom.:

779

Cov.:

AF XY:

0.0901

AC XY:

6703

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0572

Gnomad4 AMR

AF:

0.0818

Gnomad4 ASJ

AF:

0.0847

Gnomad4 EAS

AF:

0.358

Gnomad4 SAS

AF:

0.166

Gnomad4 FIN

AF:

0.0792

Gnomad4 NFE

AF:

0.0780

Gnomad4 OTH

AF:

0.0925

Alfa

AF:

0.0579

Hom.:

Bravo

AF:

0.0859

Asia WGS

AF:

0.205

AC:

713

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 03, 2018

- -

Angiokeratoma corporis diffusum with arteriovenous fistulas

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This 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 submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cerebral cavernous malformation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.9

DANN

Benign

0.87

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over