12-119688279-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001206999.2(CIT):c.6187-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00035 in 1,468,742 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.272

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 12-119688279-G-A is Benign according to our data. Variant chr12-119688279-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1217444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00187 (274/146914) while in subpopulation AFR AF= 0.0065 (253/38928). AF 95% confidence interval is 0.00584. There are 1 homozygotes in gnomad4. There are 120 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIT	NM_001206999.2	c.6187-24C>T		intron_variant		ENST00000392521.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIT	ENST00000392521.7	c.6187-24C>T		intron_variant		1	NM_001206999.2	P1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 276 AN: 146810 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.000992

GnomAD3 exomes AF: 0.000508 AC: 122 AN: 240178 Hom.: 2 AF XY: 0.000354 AC XY: 46 AN XY: 129956

Gnomad AFR exome AF: 0.00638

Gnomad AMR exome AF: 0.000639

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000185

Gnomad OTH exome AF: 0.000348

GnomAD4 exome AF: 0.000182 AC: 240 AN: 1321828 Hom.: 2 Cov.: 31 AF XY: 0.000153 AC XY: 101 AN XY: 658362

Gnomad4 AFR exome AF: 0.00639

Gnomad4 AMR exome AF: 0.000683

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000124

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000401

Gnomad4 OTH exome AF: 0.000561

GnomAD4 genome AF: 0.00187 AC: 274 AN: 146914 Hom.: 1 Cov.: 32 AF XY: 0.00167 AC XY: 120 AN XY: 71714

Gnomad4 AFR AF: 0.00650

Gnomad4 AMR AF: 0.00121

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000151

Gnomad4 OTH AF: 0.000980

Alfa AF: 0.000769 Hom.: 0

Bravo AF: 0.00216

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	3.2
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs188629304; hg19: chr12-120126084;