rs7311975

Positions:

• chr12-119713688-T-C
• chr12-119713688-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

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

Ensembl

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

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

GnomAD3 exomes AF: 0.0551 AC: 13688 AN: 248324 Hom.: 1162 AF XY: 0.0491 AC XY: 6600 AN XY: 134494

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 SAS exome AF: 0.0350

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

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.0422

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.0384

Gnomad4 SAS exome AF: 0.0350

Gnomad4 FIN exome AF: 0.0306

Gnomad4 NFE exome AF: 0.0364

Gnomad4 OTH exome AF: 0.0544

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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.0266

Gnomad4 SAS AF: 0.0337

Gnomad4 FIN AF: 0.0359

Gnomad4 NFE AF: 0.0370

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.0268 Hom.: 38

Bravo AF: 0.140

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.023
DANN	Benign	0.41

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;