dbSNP rs278126: CIT:c.5702+64C>A (chr12-119697912-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001206999.2(CIT):c.5702+64C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,612,242 control chromosomes in the GnomAD database, including 64,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5582 hom., cov: 32)

Exomes 𝑓: 0.28 ( 59125 hom. )

Consequence

CIT
NM_001206999.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.185

Variant links:

Genes affected

CIT (HGNC:1985): (citron rho-interacting serine/threonine kinase) This gene encodes a serine/threonine-protein kinase that functions in cell division. Together with the kinesin KIF14, this protein localizes to the central spindle and midbody, and functions to promote efficient cytokinesis. This protein is involved in central nervous system development. Polymorphisms in this gene are associated with bipolar disorder and risk for schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

CIT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-119697912-G-T is Benign according to our data. Variant chr12-119697912-G-T is described in ClinVar as [Benign]. Clinvar id is 1286810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIT	NM_001206999.2 link	c.5702+64C>A		intron_variant	Intron 45 of 47	ENST00000392521.7	NP_001193928.1	O14578-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIT	ENST00000392521.7 link	c.5702+64C>A		intron_variant	Intron 45 of 47	1	NM_001206999.2	ENSP00000376306.2		O14578-4

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40196

AN:

151912

Hom.:

5577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.0119

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.266

GnomAD4 exome

AF:

0.278

AC:

405479

AN:

1460212

Hom.:

59125

Cov.:

AF XY:

0.277

AC XY:

200851

AN XY:

726306

show subpopulations

Gnomad4 AFR exome

AF:

0.278

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.0163

Gnomad4 SAS exome

AF:

0.211

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.299

Gnomad4 OTH exome

AF:

0.267

GnomAD4 genome

AF:

0.264

AC:

40206

AN:

152030

Hom.:

5582

Cov.:

AF XY:

0.258

AC XY:

19179

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.259

Gnomad4 EAS

AF:

0.0120

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.245

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.262

Alfa

AF:

0.288

Hom.:

993

Bravo

AF:

0.263

Asia WGS

AF:

0.125

AC:

438

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.72

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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