chr12-119690135-C-T

Variant names:

• chr12-119690135-C-T
• rs142240301
• NM_001206999.2:c.6186+16G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001206999.2(CIT):​c.6186+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 1,455,570 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-119690135-C-T is Benign according to our data. Variant chr12-119690135-C-T is described in ClinVar as [Benign]. Clinvar id is 2857694.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00145 (221/152336) while in subpopulation AFR AF = 0.00512 (213/41572). AF 95% confidence interval is 0.00456. There are 1 homozygotes in GnomAd4. There are 99 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIT	NM_001206999.2	c.6186+16G>A		intron_variant	Intron 47 of 47	ENST00000392521.7	NP_001193928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIT	ENST00000392521.7	c.6186+16G>A		intron_variant	Intron 47 of 47	1	NM_001206999.2	ENSP00000376306.2

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 152218 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000383 AC: 47 AN: 122576 AF XY: 0.000296

Gnomad AFR exome AF: 0.00457

Gnomad AMR exome AF: 0.0000743

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000131 AC: 171 AN: 1303234 Hom.: 0 Cov.: 31 AF XY: 0.000117 AC XY: 74 AN XY: 634734

African (AFR) AF: 0.00460 AC: 123 AN: 26726

American (AMR) AF: 0.000222 AC: 5 AN: 22490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18724

East Asian (EAS) AF: 0.00 AC: 0 AN: 33260

South Asian (SAS) AF: 0.0000502 AC: 3 AN: 59734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39250

Middle Eastern (MID) AF: 0.000388 AC: 2 AN: 5154

European-Non Finnish (NFE) AF: 0.0000259 AC: 27 AN: 1043828

Other (OTH) AF: 0.000203 AC: 11 AN: 54068

GnomAD4 genome AF: 0.00145 AC: 221 AN: 152336 Hom.: 1 Cov.: 31 AF XY: 0.00133 AC XY: 99 AN XY: 74496

African (AFR) AF: 0.00512 AC: 213 AN: 41572

American (AMR) AF: 0.000261 AC: 4 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000500 Hom.: 0

Bravo AF: 0.00154

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.36
PhyloP100		1.2
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: rs142240301; hg19: chr12-120127940;