12-119805261-C-G

Variant names:

• chr12-119805261-C-G
• rs10744743
• NM_001206999.2:c.1112-1872G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206999.2(CIT):​c.1112-1872G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,028 control chromosomes in the GnomAD database, including 27,774 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (27774 hom., cov: 32)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIT	NM_001206999.2	MANE Select	c.1112-1872G>C		intron	N/A	NP_001193928.1	O14578-4
	CIT	NM_007174.3		c.1112-1872G>C		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.1112-1872G>C		intron	N/A	ENSP00000376306.2	O14578-4
	CIT	ENST00000261833.11	TSL:1	c.1112-1872G>C		intron	N/A	ENSP00000261833.7	O14578-1
	CIT	ENST00000928243.1		c.1112-1872G>C		intron	N/A	ENSP00000598302.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89878 AN: 151910 Hom.: 27762 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.591 AC: 89917 AN: 152028 Hom.: 27774 Cov.: 32 AF XY: 0.599 AC XY: 44528 AN XY: 74298

African (AFR) AF: 0.409 AC: 16938 AN: 41438

American (AMR) AF: 0.714 AC: 10913 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2447 AN: 3470

East Asian (EAS) AF: 0.837 AC: 4326 AN: 5168

South Asian (SAS) AF: 0.714 AC: 3439 AN: 4814

European-Finnish (FIN) AF: 0.669 AC: 7060 AN: 10560

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42590 AN: 67976

Other (OTH) AF: 0.634 AC: 1339 AN: 2112

Alfa AF: 0.595 Hom.: 3413

Bravo AF: 0.590

Asia WGS AF: 0.771 AC: 2679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		0.064
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: rs10744743; hg19: chr12-120243065;