12-119689930-C-T

Variant names:

• chr12-119689930-C-T
• rs111356250
• NM_001206999.2:c.6186+221G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001206999.2(CIT):​c.6186+221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 152,262 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.026 (74 hom., cov: 31)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.212
• Publications: 0 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.91).
• BP6: Variant 12-119689930-C-T is Benign according to our data. Variant chr12-119689930-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1202291.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0261 (3976/152262) while in subpopulation AFR AF = 0.0409 (1702/41566). AF 95% confidence interval is 0.0393. There are 74 homozygotes in GnomAd4. There are 1904 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 74 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIT	NM_001206999.2	MANE Select	c.6186+221G>A		intron	N/A	NP_001193928.1	O14578-4
	CIT	NM_007174.3		c.6060+221G>A		intron	N/A	NP_009105.1	O14578-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIT	ENST00000392521.7	TSL:1 MANE Select	c.6186+221G>A		intron	N/A	ENSP00000376306.2	O14578-4
	CIT	ENST00000261833.11	TSL:1	c.6060+221G>A		intron	N/A	ENSP00000261833.7	O14578-1
	CIT	ENST00000928243.1		c.6183+221G>A		intron	N/A	ENSP00000598302.1

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3964 AN: 152144 Hom.: 73 Cov.: 31

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.0222

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0240

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

GnomAD4 genome AF: 0.0261 AC: 3976 AN: 152262 Hom.: 74 Cov.: 31 AF XY: 0.0256 AC XY: 1904 AN XY: 74440

African (AFR) AF: 0.0409 AC: 1702 AN: 41566

American (AMR) AF: 0.0247 AC: 378 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.0223 AC: 115 AN: 5168

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4832

European-Finnish (FIN) AF: 0.0203 AC: 215 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0209 AC: 1419 AN: 68008

Other (OTH) AF: 0.0233 AC: 49 AN: 2106

Alfa AF: 0.0130 Hom.: 4

Bravo AF: 0.0259

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.83
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

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: rs111356250; hg19: chr12-120127735;