12-119840528-C-T

Position:

• chr12-119840528-C-T

Variant summary

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

The NM_001206999.2(CIT):​c.517-6300G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,996 control chromosomes in the GnomAD database, including 16,965 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 0.46 (16965 hom., cov: 32)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601

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=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIT	NM_001206999.2	c.517-6300G>A		intron_variant		ENST00000392521.7	NP_001193928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIT	ENST00000392521.7	c.517-6300G>A		intron_variant		1	NM_001206999.2	ENSP00000376306.2
CIT	ENST00000261833.11	c.517-6300G>A		intron_variant		1		ENSP00000261833.7
CIT	ENST00000536325.1	c.267+9646G>A		intron_variant		3		ENSP00000443199.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70036 AN: 151878 Hom.: 16946 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.461 AC: 70096 AN: 151996 Hom.: 16965 Cov.: 32 AF XY: 0.466 AC XY: 34632 AN XY: 74290

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.506

Alfa AF: 0.434 Hom.: 3025

Bravo AF: 0.451

Asia WGS AF: 0.526 AC: 1829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.3
DANN	Benign	0.68

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: rs4766951; hg19: chr12-120278332;