12-119842848-T-C

Variant names:

• chr12-119842848-T-C
• rs10774517
• NM_001206999.2:c.516+7326A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 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.516+7326A>G		intron	N/A	NP_001193928.1
	CIT	NM_007174.3		c.516+7326A>G		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.516+7326A>G		intron	N/A	ENSP00000376306.2
	CIT	ENST00000261833.11	TSL:1	c.516+7326A>G		intron	N/A	ENSP00000261833.7
	CIT	ENST00000536325.1	TSL:3	c.267+7326A>G		intron	N/A	ENSP00000443199.1

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

African (AFR) AF: 0.112 AC: 4653 AN: 41550

American (AMR) AF: 0.247 AC: 3773 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3468

East Asian (EAS) AF: 0.444 AC: 2294 AN: 5172

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4828

European-Finnish (FIN) AF: 0.217 AC: 2302 AN: 10596

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13685 AN: 68002

Other (OTH) AF: 0.181 AC: 382 AN: 2114

Alfa AF: 0.196 Hom.: 7547

Bravo AF: 0.191

Asia WGS AF: 0.314 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.077
DANN	Benign	0.56
PhyloP100		-2.6
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: rs10774517; hg19: chr12-120280652;