rs202983

Variant names:

• chr12-119724541-G-A
• rs202983
• NM_001206999.2:c.3592-3092C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.85).
• 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 rank	MANE	Protein	UniProt
CIT	NM_001206999.2	c.3592-3092C>T		intron_variant	Intron 28 of 47	ENST00000392521.7	NP_001193928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIT	ENST00000392521.7	c.3592-3092C>T		intron_variant	Intron 28 of 47	1	NM_001206999.2	ENSP00000376306.2

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

African (AFR) AF: 0.237 AC: 9835 AN: 41452

American (AMR) AF: 0.217 AC: 3313 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3468

East Asian (EAS) AF: 0.0771 AC: 399 AN: 5172

South Asian (SAS) AF: 0.194 AC: 934 AN: 4812

European-Finnish (FIN) AF: 0.227 AC: 2403 AN: 10568

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19156 AN: 67972

Other (OTH) AF: 0.252 AC: 532 AN: 2110

Alfa AF: 0.271 Hom.: 24242

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
PhyloP100		1.4
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: rs202983; hg19: chr12-120162346;