7-92246057-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019004.2(ANKIB1):c.-553G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 279,536 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 203 hom., cov: 31)

Exomes 𝑓: 0.00073 ( 3 hom. )

Consequence

ANKIB1
NM_019004.2 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.29

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

cerebral cavernous malformation 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
famililal cerebral cavernous malformations
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KRIT1 links:

ENSG00000289027 (HGNC:):

ENSG00000289027 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-92246057-G-A is Benign according to our data. Variant chr7-92246057-G-A is described in ClinVar as Benign. ClinVar VariationId is 360908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019004.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKIB1	NM_019004.2	MANE Select	c.-553G>A	5_prime_UTR	Exon 1 of 20	NP_061877.1	Q9P2G1
KRIT1	NM_001350672.1		c.-154C>T	5_prime_UTR	Exon 1 of 17	NP_001337601.1	O00522-1
KRIT1	NM_001350673.1		c.-424C>T	5_prime_UTR	Exon 1 of 18	NP_001337602.1	O00522-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKIB1	ENST00000265742.8	TSL:1 MANE Select	c.-553G>A	5_prime_UTR	Exon 1 of 20	ENSP00000265742.3	Q9P2G1
KRIT1	ENST00000340022.6	TSL:1	c.-976C>T	5_prime_UTR	Exon 1 of 19	ENSP00000344668.2	O00522-1
KRIT1	ENST00000458177.7	TSL:1	c.-572C>T	5_prime_UTR	Exon 1 of 19	ENSP00000391675.2	O00522-1

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

4367

AN:

152144

Hom.:

202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0220

GnomAD4 exome

AF:

0.000731

AC:

AN:

127278

Hom.:

Cov.:

AF XY:

0.000772

AC XY:

AN XY:

72510

show subpopulations

African (AFR)

AF:

0.0895

AC:

AN:

626

American (AMR)

AF:

0.00593

AC:

AN:

1012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2518

East Asian (EAS)

AF:

0.00

AC:

AN:

798

South Asian (SAS)

AF:

0.000129

AC:

AN:

31074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8118

Middle Eastern (MID)

AF:

0.00412

AC:

AN:

486

European-Non Finnish (NFE)

AF:

0.0000524

AC:

AN:

76400

Other (OTH)

AF:

0.00336

AC:

AN:

6246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0287

AC:

4376

AN:

152258

Hom.:

203

Cov.:

AF XY:

0.0285

AC XY:

2121

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.100

AC:

4159

AN:

41532

American (AMR)

AF:

0.0101

AC:

155

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68014

Other (OTH)

AF:

0.0218

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

209

419

628

838

1047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0181

Hom.:

Bravo

AF:

0.0321

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Angiokeratoma corporis diffusum with arteriovenous fistulas (1)

Cerebral cavernous malformation (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.53

PhyloP100

1.3

PromoterAI

-0.0085

Neutral

(source)

Mutation Taster

=294/6

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over