12-119772533-G-A

Variant names:

• chr12-119772533-G-A
• rs203332
• NM_001206999.2:c.2082+237C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001206999.2(CIT):​c.2082+237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,082 control chromosomes in the GnomAD database, including 20,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (20017 hom., cov: 32)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.829
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly 17, primary, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 12-119772533-G-A is Benign according to our data. Variant chr12-119772533-G-A is described in ClinVar as Benign. ClinVar VariationId is 1240491.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206999.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIT	NM_001206999.2	MANE Select	c.2082+237C>T		intron	N/A	NP_001193928.1
	CIT	NM_007174.3		c.2082+237C>T		intron	N/A	NP_009105.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIT	ENST00000392521.7	TSL:1 MANE Select	c.2082+237C>T		intron	N/A	ENSP00000376306.2
	CIT	ENST00000261833.11	TSL:1	c.2082+237C>T		intron	N/A	ENSP00000261833.7
	CIT	ENST00000679061.1		n.1214C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77444 AN: 151964 Hom.: 20001 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.530

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.510 AC: 77505 AN: 152082 Hom.: 20017 Cov.: 32 AF XY: 0.510 AC XY: 37890 AN XY: 74322

African (AFR) AF: 0.516 AC: 21425 AN: 41490

American (AMR) AF: 0.588 AC: 8992 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3470

East Asian (EAS) AF: 0.492 AC: 2541 AN: 5168

South Asian (SAS) AF: 0.544 AC: 2620 AN: 4818

European-Finnish (FIN) AF: 0.513 AC: 5424 AN: 10568

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32902 AN: 67970

Other (OTH) AF: 0.528 AC: 1114 AN: 2110

Alfa AF: 0.506 Hom.: 3355

Bravo AF: 0.516

Asia WGS AF: 0.535 AC: 1860 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.63
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs203332; hg19: chr12-120210337;