rs3847960

Variant names:

• chr12-119833296-T-A
• rs3847960
• NM_001206999.2:c.660-432A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-119833296-T-A
• chr12-119833296-T-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.660-432A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,976 control chromosomes in the GnomAD database, including 28,618 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 0.61 (28618 hom., cov: 31)
• Consequence: CIT NM_001206999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.467
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIT	NM_001206999.2	c.660-432A>T		intron_variant	Intron 6 of 47	ENST00000392521.7	NP_001193928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIT	ENST00000392521.7	c.660-432A>T		intron_variant	Intron 6 of 47	1	NM_001206999.2	ENSP00000376306.2
CIT	ENST00000261833.11	c.660-432A>T		intron_variant	Intron 6 of 46	1		ENSP00000261833.7
CIT	ENST00000536325.1	c.267+16878A>T		intron_variant	Intron 2 of 2	3		ENSP00000443199.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92063 AN: 151858 Hom.: 28599 Cov.: 31

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.631

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.606 AC: 92121 AN: 151976 Hom.: 28618 Cov.: 31 AF XY: 0.613 AC XY: 45553 AN XY: 74294

African (AFR) AF: 0.475 AC: 19667 AN: 41444

American (AMR) AF: 0.707 AC: 10794 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2422 AN: 3470

East Asian (EAS) AF: 0.836 AC: 4320 AN: 5168

South Asian (SAS) AF: 0.709 AC: 3421 AN: 4822

European-Finnish (FIN) AF: 0.667 AC: 7026 AN: 10534

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42274 AN: 67954

Other (OTH) AF: 0.636 AC: 1343 AN: 2112

Alfa AF: 0.603 Hom.: 3462

Bravo AF: 0.607

Asia WGS AF: 0.775 AC: 2693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.71
PhyloP100		0.47
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: rs3847960; hg19: chr12-120271100;