rs17496224

Variant names:

• chr12-119856044-C-T
• rs17496224
• NM_001206999.2:c.414+1479G>A

Variant summary

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

The NM_001206999.2(CIT):​c.414+1479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 152,280 control chromosomes in the GnomAD database, including 158 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 0.040 (158 hom., cov: 32)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925
• Publications: 3 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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206999.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIT	NM_001206999.2	MANE Select	c.414+1479G>A		intron	N/A	NP_001193928.1
	CIT	NM_007174.3		c.414+1479G>A		intron	N/A	NP_009105.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIT	ENST00000392521.7	TSL:1 MANE Select	c.414+1479G>A		intron	N/A	ENSP00000376306.2
	CIT	ENST00000261833.11	TSL:1	c.414+1479G>A		intron	N/A	ENSP00000261833.7
	CIT	ENST00000536325.1	TSL:3	c.165+1479G>A		intron	N/A	ENSP00000443199.1

Frequencies

GnomAD3 genomes AF: 0.0402 AC: 6124 AN: 152162 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0471

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.0460

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

GnomAD4 genome AF: 0.0402 AC: 6117 AN: 152280 Hom.: 158 Cov.: 32 AF XY: 0.0401 AC XY: 2986 AN XY: 74458

African (AFR) AF: 0.0103 AC: 428 AN: 41568

American (AMR) AF: 0.0335 AC: 512 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0454 AC: 219 AN: 4826

European-Finnish (FIN) AF: 0.0471 AC: 500 AN: 10616

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0583 AC: 3967 AN: 68018

Other (OTH) AF: 0.0455 AC: 96 AN: 2110

Alfa AF: 0.0549 Hom.: 199

Bravo AF: 0.0375

Asia WGS AF: 0.0250 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.80
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism

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: rs17496224; hg19: chr12-120293848;