chr12-119690277-T-C

Variant names:

• chr12-119690277-T-C
• rs150770539
• NM_001206999.2:c.6060A>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001206999.2(CIT):​c.6060A>G​(p.Arg2020Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,579,456 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (68 hom.)
• Consequence: CIT NM_001206999.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.473
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.055).
• BP6: Variant 12-119690277-T-C is Benign according to our data. Variant chr12-119690277-T-C is described in ClinVar as Benign. ClinVar VariationId is 713252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.473 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0505 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.6060A>G	p.Arg2020Arg	synonymous	Exon 47 of 48	NP_001193928.1	O14578-4
	CIT	NM_007174.3		c.5934A>G	p.Arg1978Arg	synonymous	Exon 46 of 47	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.6060A>G	p.Arg2020Arg	synonymous	Exon 47 of 48	ENSP00000376306.2	O14578-4
	CIT	ENST00000261833.11	TSL:1	c.5934A>G	p.Arg1978Arg	synonymous	Exon 46 of 47	ENSP00000261833.7	O14578-1
	CIT	ENST00000928243.1		c.6057A>G	p.Arg2019Arg	synonymous	Exon 47 of 48	ENSP00000598302.1

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 194 AN: 152174 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0307

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00248 AC: 524 AN: 211288 AF XY: 0.00212

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000366

Gnomad ASJ exome AF: 0.00137

Gnomad EAS exome AF: 0.0289

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000180

Gnomad OTH exome AF: 0.00154

GnomAD4 exome AF: 0.00171 AC: 2436 AN: 1427164 Hom.: 68 Cov.: 31 AF XY: 0.00164 AC XY: 1168 AN XY: 710412

African (AFR) AF: 0.00 AC: 0 AN: 31836

American (AMR) AF: 0.0000519 AC: 2 AN: 38536

Ashkenazi Jewish (ASJ) AF: 0.00275 AC: 69 AN: 25130

East Asian (EAS) AF: 0.0524 AC: 2029 AN: 38756

South Asian (SAS) AF: 0.000656 AC: 55 AN: 83798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40132

Middle Eastern (MID) AF: 0.000530 AC: 3 AN: 5658

European-Non Finnish (NFE) AF: 0.000199 AC: 220 AN: 1103994

Other (OTH) AF: 0.000978 AC: 58 AN: 59324

GnomAD4 genome AF: 0.00127 AC: 194 AN: 152292 Hom.: 5 Cov.: 31 AF XY: 0.00148 AC XY: 110 AN XY: 74466

African (AFR) AF: 0.0000241 AC: 1 AN: 41566

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3464

East Asian (EAS) AF: 0.0308 AC: 159 AN: 5162

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000506 Hom.: 0

Bravo AF: 0.00131

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.0
DANN	Benign	0.67
PhyloP100		-0.47
Mutation Taster		=76/24	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: rs150770539; hg19: chr12-120128082; COSMIC: COSV107241127; COSMIC: COSV107241127;