rs202984

Variant names:

• chr12-119747149-A-G
• rs202984
• NM_001206999.2:c.2905-4685T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206999.2(CIT):​c.2905-4685T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,172 control chromosomes in the GnomAD database, including 45,499 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 0.77 (45499 hom., cov: 32)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 2 publications found

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]

CIT Gene-Disease associations (from GenCC):

• microcephaly 17, primary, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIT	NM_001206999.2	c.2905-4685T>C		intron_variant	Intron 23 of 47	ENST00000392521.7	NP_001193928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIT	ENST00000392521.7	c.2905-4685T>C		intron_variant	Intron 23 of 47	1	NM_001206999.2	ENSP00000376306.2

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117260 AN: 152054 Hom.: 45461 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.799

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

GnomAD4 genome AF: 0.771 AC: 117353 AN: 152172 Hom.: 45499 Cov.: 32 AF XY: 0.769 AC XY: 57207 AN XY: 74398

African (AFR) AF: 0.746 AC: 30976 AN: 41514

American (AMR) AF: 0.823 AC: 12587 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2866 AN: 3472

East Asian (EAS) AF: 0.533 AC: 2755 AN: 5172

South Asian (SAS) AF: 0.755 AC: 3642 AN: 4824

European-Finnish (FIN) AF: 0.804 AC: 8519 AN: 10590

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53525 AN: 67994

Other (OTH) AF: 0.795 AC: 1677 AN: 2110

Alfa AF: 0.781 Hom.: 6016

Bravo AF: 0.772

Asia WGS AF: 0.671 AC: 2338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.37
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs202984; hg19: chr12-120184954;