Genetic Variant NM_001206999.2:c.1545+76G>A (chr12-119783832-C-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.1545+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,478,510 control chromosomes in the GnomAD database, including 149,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13288 hom., cov: 32)

Exomes 𝑓: 0.45 ( 136395 hom. )

Consequence

CIT
NM_001206999.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.74

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=-0.67).

BP6

Variant 12-119783832-C-T is Benign according to our data. Variant chr12-119783832-C-T is described in ClinVar as [Benign]. Clinvar id is 1179805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIT	NM_001206999.2 link	c.1545+76G>A		intron_variant	Intron 12 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.1545+76G>A		intron_variant	Intron 12 of 47	1	NM_001206999.2	ENSP00000376306.2		O14578-4

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61235

AN:

151876

Hom.:

13291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.242

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.536

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.485

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.445

GnomAD4 exome

AF:

0.451

AC:

598677

AN:

1326516

Hom.:

136395

Cov.:

AF XY:

0.452

AC XY:

294257

AN XY:

651274

show subpopulations

Gnomad4 AFR exome

AF:

0.240

Gnomad4 AMR exome

AF:

0.564

Gnomad4 ASJ exome

AF:

0.539

Gnomad4 EAS exome

AF:

0.395

Gnomad4 SAS exome

AF:

0.455

Gnomad4 FIN exome

AF:

0.481

Gnomad4 NFE exome

AF:

0.453

Gnomad4 OTH exome

AF:

0.453

GnomAD4 genome

AF:

0.403

AC:

61240

AN:

151994

Hom.:

13288

Cov.:

AF XY:

0.406

AC XY:

30136

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.242

Gnomad4 AMR

AF:

0.533

Gnomad4 ASJ

AF:

0.536

Gnomad4 EAS

AF:

0.399

Gnomad4 SAS

AF:

0.451

Gnomad4 FIN

AF:

0.485

Gnomad4 NFE

AF:

0.448

Gnomad4 OTH

AF:

0.442

Alfa

AF:

0.449

Hom.:

26394

Bravo

AF:

0.403

Asia WGS

AF:

0.449

AC:

1562

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 06, 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

-0.67

CADD

Benign

DANN

Benign

0.79

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