5-132747849-C-A

Variant names:

• chr5-132747849-C-A
• rs890476605
• NM_001039780.4:c.354C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039780.4(CCNI2):​c.354C>A​(p.Asp118Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,320,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D118V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: CCNI2 NM_001039780.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.95
• Publications: 0 publications found

Genes affected

CCNI2 (HGNC:33869): (cyclin I family member 2) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in mitotic cell cycle phase transition and regulation of cyclin-dependent protein serine/threonine kinase activity. Predicted to be part of cyclin-dependent protein kinase holoenzyme complex. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073183596).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039780.4. 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
	CCNI2	NM_001039780.4	MANE Select	c.354C>A	p.Asp118Glu	missense	Exon 1 of 6	NP_001034869.1	Q6ZMN8-1
	CCNI2	NM_001287252.2		c.354C>A	p.Asp118Glu	missense	Exon 1 of 6	NP_001274181.1	Q6ZMN8-2
	CCNI2	NM_001287253.2		c.354C>A	p.Asp118Glu	missense	Exon 1 of 6	NP_001274182.1	Q6ZMN8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNI2	ENST00000378731.6	TSL:1 MANE Select	c.354C>A	p.Asp118Glu	missense	Exon 1 of 6	ENSP00000368005.1	Q6ZMN8-1
	CCNI2	ENST00000614847.1	TSL:1	c.354C>A	p.Asp118Glu	missense	Exon 1 of 6	ENSP00000478257.1	Q6ZMN8-2
	CCNI2	ENST00000878149.1		c.354C>A	p.Asp118Glu	missense	Exon 1 of 6	ENSP00000548208.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000182 AC: 24 AN: 1320250 Hom.: 0 Cov.: 31 AF XY: 0.0000154 AC XY: 10 AN XY: 650226

African (AFR) AF: 0.00 AC: 0 AN: 26686

American (AMR) AF: 0.00 AC: 0 AN: 25870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22950

East Asian (EAS) AF: 0.00 AC: 0 AN: 29338

South Asian (SAS) AF: 0.00 AC: 0 AN: 71834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4450

European-Non Finnish (NFE) AF: 0.0000228 AC: 24 AN: 1051480

Other (OTH) AF: 0.00 AC: 0 AN: 54876

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.13
DANN	Benign	0.69
DEOGEN2	Benign	0.00069	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.81	L
PhyloP100		-1.9
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.031
Sift	Benign	0.38	T
Sift4G	Benign	0.56	T
Polyphen		0.11	B
Vest4		0.067
MutPred		0.53		Loss of helix (P = 0.1706)
MVP		0.21
MPC		1.3
ClinPred		0.046	T
GERP RS		-1.1
PromoterAI		0.019	Neutral
Varity_R		0.033
gMVP		0.10
Mutation Taster		=98/2	polymorphism

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: rs890476605; hg19: chr5-132083541;