12-119688269-A-AAGG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001206999.2(CIT):c.6187-15_6187-14insCCT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,610,176 control chromosomes in the GnomAD database, including 106,426 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12872 hom., cov: 0)
  • Exomes 𝑓: 0.35 (93554 hom.)
• Consequence: CIT NM_001206999.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.78

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 12-119688269-A-AAGG is Benign according to our data. Variant chr12-119688269-A-AAGG is described in ClinVar as [Benign]. Clinvar id is 1264110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIT	NM_001206999.2	c.6187-15_6187-14insCCT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000392521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIT	ENST00000392521.7	c.6187-15_6187-14insCCT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001206999.2	P1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59786 AN: 151896 Hom.: 12854 Cov.: 0

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.0407

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.386

GnomAD3 exomes AF: 0.311 AC: 78159 AN: 251202 Hom.: 13969 AF XY: 0.312 AC XY: 42429 AN XY: 135774

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.225

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.0352

Gnomad SAS exome AF: 0.246

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.367

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.349 AC: 509200 AN: 1458162 Hom.: 93554 Cov.: 31 AF XY: 0.347 AC XY: 251829 AN XY: 725606

Gnomad4 AFR exome AF: 0.563

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.0563

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.346

GnomAD4 genome AF: 0.394 AC: 59849 AN: 152014 Hom.: 12872 Cov.: 0 AF XY: 0.384 AC XY: 28540 AN XY: 74322

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.0408

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.380

Asia WGS AF: 0.169 AC: 592 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10669112; hg19: chr12-120126074;