5-132747724-C-T

Variant names:

• chr5-132747724-C-T
• rs1561723883
• NM_001039780.4:c.229C>T

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.229C>T​(p.Arg77Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 1,329,994 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R77G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CCNI2 NM_001039780.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598
• 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=0.100465685).

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.229C>T	p.Arg77Trp	missense	Exon 1 of 6	NP_001034869.1	Q6ZMN8-1
	CCNI2	NM_001287252.2		c.229C>T	p.Arg77Trp	missense	Exon 1 of 6	NP_001274181.1	Q6ZMN8-2
	CCNI2	NM_001287253.2		c.229C>T	p.Arg77Trp	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.229C>T	p.Arg77Trp	missense	Exon 1 of 6	ENSP00000368005.1	Q6ZMN8-1
	CCNI2	ENST00000614847.1	TSL:1	c.229C>T	p.Arg77Trp	missense	Exon 1 of 6	ENSP00000478257.1	Q6ZMN8-2
	CCNI2	ENST00000878149.1		c.229C>T	p.Arg77Trp	missense	Exon 1 of 6	ENSP00000548208.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000226 AC: 3 AN: 1329994 Hom.: 0 Cov.: 31 AF XY: 0.00000458 AC XY: 3 AN XY: 655302

African (AFR) AF: 0.0000371 AC: 1 AN: 26950

American (AMR) AF: 0.00 AC: 0 AN: 28040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23160

East Asian (EAS) AF: 0.0000336 AC: 1 AN: 29766

South Asian (SAS) AF: 0.0000137 AC: 1 AN: 73236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3950

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056214

Other (OTH) AF: 0.00 AC: 0 AN: 55374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.0
DANN	Benign	0.93
DEOGEN2	Benign	0.00078	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.60
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.037
Sift	Benign	0.085	T
Sift4G	Uncertain	0.023	D
Polyphen		0.81	P
Vest4		0.14
MutPred		0.29		Loss of methylation at R80 (P = 0.093)
MVP		0.10
MPC		1.3
ClinPred		0.84	D
GERP RS		-3.1
PromoterAI		-0.055	Neutral
Varity_R		0.053
gMVP		0.17
Mutation Taster		=99/1	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: rs1561723883; hg19: chr5-132083416;