12-119842848-T-C

Position:

• chr12-119842848-T-C

Variant summary

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

The NM_001206999.2(CIT):​c.516+7326A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,202 control chromosomes in the GnomAD database, including 3,189 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 0.19 (3189 hom., cov: 32)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.61

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIT	NM_001206999.2	c.516+7326A>G		intron_variant		ENST00000392521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIT	ENST00000392521.7	c.516+7326A>G		intron_variant		1	NM_001206999.2	P1
CIT	ENST00000261833.11	c.516+7326A>G		intron_variant		1
CIT	ENST00000536325.1	c.267+7326A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29093 AN: 152084 Hom.: 3189 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.191 AC: 29113 AN: 152202 Hom.: 3189 Cov.: 32 AF XY: 0.197 AC XY: 14657 AN XY: 74412

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.181

Alfa AF: 0.195 Hom.: 2641

Bravo AF: 0.191

Asia WGS AF: 0.314 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.077
DANN	Benign	0.56

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: rs10774517; hg19: chr12-120280652;