12-119713688-T-G

Position:

• chr12-119713688-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001206999.2(CIT):​c.4307-40A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,603,496 control chromosomes in the GnomAD database, including 82 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 0.013 (47 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (35 hom.)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1979/152294) while in subpopulation AFR AF= 0.0457 (1900/41548). AF 95% confidence interval is 0.044. There are 47 homozygotes in gnomad4. There are 936 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIT	NM_001206999.2	c.4307-40A>C		intron_variant		ENST00000392521.7	NP_001193928.1
MIR1178	NR_031589.1	n.37A>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIT	ENST00000392521.7	c.4307-40A>C		intron_variant		1	NM_001206999.2	ENSP00000376306	P1
MIR1178	ENST00000408396.1	n.37A>C		mature_miRNA_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1980 AN: 152176 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00324 AC: 805 AN: 248324 Hom.: 20 AF XY: 0.00248 AC XY: 333 AN XY: 134494

Gnomad AFR exome AF: 0.0439

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000811

Gnomad OTH exome AF: 0.000985

GnomAD4 exome AF: 0.00125 AC: 1821 AN: 1451202 Hom.: 35 Cov.: 28 AF XY: 0.00107 AC XY: 775 AN XY: 722660

Gnomad4 AFR exome AF: 0.0456

Gnomad4 AMR exome AF: 0.00213

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000263

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.0130 AC: 1979 AN: 152294 Hom.: 47 Cov.: 33 AF XY: 0.0126 AC XY: 936 AN XY: 74476

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.000503 Hom.: 38

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.022
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs7311975; hg19: chr12-120151493;