rs202983

Positions:

• chr12-119724541-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206999.2(CIT):​c.3592-3092C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,028 control chromosomes in the GnomAD database, including 4,854 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 0.25 (4854 hom., cov: 31)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIT	NM_001206999.2	c.3592-3092C>T		intron_variant		ENST00000392521.7	NP_001193928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIT	ENST00000392521.7	c.3592-3092C>T		intron_variant		1	NM_001206999.2	ENSP00000376306	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37636 AN: 151910 Hom.: 4849 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0768

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.248 AC: 37653 AN: 152028 Hom.: 4854 Cov.: 31 AF XY: 0.242 AC XY: 17973 AN XY: 74320

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.0771

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.252

Alfa AF: 0.276 Hom.: 11866

Bravo AF: 0.247

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs202983; hg19: chr12-120162346;