dbSNP rs17496224: CIT:c.414+1479G>A (chr12-119856044-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001206999.2(CIT):c.414+1479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 152,280 control chromosomes in the GnomAD database, including 158 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 0.040 ( 158 hom., cov: 32)

Consequence

CIT
NM_001206999.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.925

Publications

3 publications found

Variant links:

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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CIT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0568 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIT	NM_001206999.2	MANE Select	c.414+1479G>A		intron	N/A	NP_001193928.1	O14578-4
	CIT	NM_007174.3		c.414+1479G>A		intron	N/A	NP_009105.1	O14578-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CIT	ENST00000392521.7	TSL:1 MANE Select	c.414+1479G>A	intron	N/A	ENSP00000376306.2	O14578-4
CIT	ENST00000261833.11	TSL:1	c.414+1479G>A	intron	N/A	ENSP00000261833.7	O14578-1
CIT	ENST00000928243.1		c.414+1479G>A	intron	N/A	ENSP00000598302.1

Frequencies

GnomAD3 genomes

AF:

0.0402

AC:

6124

AN:

152162

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0336

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0462

Gnomad FIN

AF:

0.0471

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0583

Gnomad OTH

AF:

0.0460

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

GnomAD4 genome

AF:

0.0402

AC:

6117

AN:

152280

Hom.:

158

Cov.:

AF XY:

0.0401

AC XY:

2986

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0103

AC:

428

AN:

41568

American (AMR)

AF:

0.0335

AC:

512

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

351

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.0454

AC:

219

AN:

4826

European-Finnish (FIN)

AF:

0.0471

AC:

500

AN:

10616

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0583

AC:

3967

AN:

68018

Other (OTH)

AF:

0.0455

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

298

596

893

1191

1489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0549

Hom.:

199

Bravo

AF:

0.0375

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.93

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over