12-119713688-T-C

Variant names:

• chr12-119713688-T-C
• rs7311975
• NM_001206999.2:c.4307-40A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001206999.2(CIT):​c.4307-40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 1,603,300 control chromosomes in the GnomAD database, including 5,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2616 hom., cov: 33)
  • Exomes 𝑓: 0.044 (3299 hom.)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.54
• Publications: 16 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]

MIR1178 (HGNC:35259): (microRNA 1178) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-119713688-T-C is Benign according to our data. Variant chr12-119713688-T-C is described in ClinVar as Benign. ClinVar VariationId is 1279215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 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.4307-40A>G		intron	N/A	NP_001193928.1
	MIR1178	NR_031589.1		n.37A>G		non_coding_transcript_exon	Exon 1 of 1
	CIT	NM_007174.3		c.4181-40A>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.4307-40A>G		intron	N/A	ENSP00000376306.2
	CIT	ENST00000261833.11	TSL:1	c.4181-40A>G		intron	N/A	ENSP00000261833.7
	MIR1178	ENST00000408396.1	TSL:6	n.37A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18809 AN: 152150 Hom.: 2604 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.0339

Gnomad FIN AF: 0.0359

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0370

Gnomad OTH AF: 0.0966

GnomAD2 exomes AF: 0.0551 AC: 13688 AN: 248324 AF XY: 0.0491

Gnomad AFR exome AF: 0.351

Gnomad AMR exome AF: 0.0406

Gnomad ASJ exome AF: 0.0136

Gnomad EAS exome AF: 0.0224

Gnomad FIN exome AF: 0.0331

Gnomad NFE exome AF: 0.0362

Gnomad OTH exome AF: 0.0428

GnomAD4 exome AF: 0.0440 AC: 63895 AN: 1451032 Hom.: 3299 Cov.: 28 AF XY: 0.0427 AC XY: 30886 AN XY: 722578

African (AFR) AF: 0.356 AC: 11864 AN: 33286

American (AMR) AF: 0.0422 AC: 1884 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 323 AN: 26064

East Asian (EAS) AF: 0.0384 AC: 1521 AN: 39658

South Asian (SAS) AF: 0.0350 AC: 3009 AN: 85956

European-Finnish (FIN) AF: 0.0306 AC: 1632 AN: 53362

Middle Eastern (MID) AF: 0.0486 AC: 279 AN: 5744

European-Non Finnish (NFE) AF: 0.0364 AC: 40114 AN: 1102220

Other (OTH) AF: 0.0544 AC: 3269 AN: 60048

GnomAD4 genome AF: 0.124 AC: 18862 AN: 152268 Hom.: 2616 Cov.: 33 AF XY: 0.122 AC XY: 9050 AN XY: 74468

African (AFR) AF: 0.345 AC: 14347 AN: 41526

American (AMR) AF: 0.0677 AC: 1035 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3468

East Asian (EAS) AF: 0.0266 AC: 138 AN: 5186

South Asian (SAS) AF: 0.0337 AC: 163 AN: 4830

European-Finnish (FIN) AF: 0.0359 AC: 382 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0370 AC: 2516 AN: 68014

Other (OTH) AF: 0.0956 AC: 202 AN: 2114

Alfa AF: 0.0268 Hom.: 38

Bravo AF: 0.140

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.023
DANN	Benign	0.41
PhyloP100		-3.5
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: rs7311975; hg19: chr12-120151493;