rs4252821

Variant names:

• chr4-77066695-T-C
• rs4252821
• NM_006835.3:c.-43-290A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006835.3(CCNI):​c.-43-290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00698 in 152,310 control chromosomes in the GnomAD database, including 24 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 0.0070 (24 hom., cov: 32)
• Consequence: CCNI NM_006835.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 1 publications found

Genes affected

CCNI (HGNC:1595): (cyclin I) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin shows the highest similarity with cyclin G. The transcript of this gene was found to be expressed constantly during cell cycle progression. [provided by RefSeq, Jan 2017]

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 = 0.0678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006835.3. 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
	CCNI	NM_006835.3	MANE Select	c.-43-290A>G		intron	N/A	NP_006826.1	Q14094-1
	CCNI	NM_001348132.2		c.-39-294A>G		intron	N/A	NP_001335061.1	Q14094-1
	CCNI	NM_001348133.2		c.-43-290A>G		intron	N/A	NP_001335062.1	Q14094-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNI	ENST00000237654.9	TSL:1 MANE Select	c.-43-290A>G		intron	N/A	ENSP00000237654.4	Q14094-1
	CCNI	ENST00000950261.1		c.-333A>G		5_prime_UTR	Exon 1 of 6	ENSP00000620320.1
	CCNI	ENST00000718433.1		c.-39-294A>G		intron	N/A	ENSP00000520818.1	Q14094-1

Frequencies

GnomAD3 genomes AF: 0.00696 AC: 1060 AN: 152192 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.00813

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

GnomAD4 genome AF: 0.00698 AC: 1063 AN: 152310 Hom.: 24 Cov.: 32 AF XY: 0.00832 AC XY: 620 AN XY: 74480

African (AFR) AF: 0.00132 AC: 55 AN: 41576

American (AMR) AF: 0.0215 AC: 329 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0739 AC: 383 AN: 5186

South Asian (SAS) AF: 0.00745 AC: 36 AN: 4830

European-Finnish (FIN) AF: 0.0163 AC: 173 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00104 AC: 71 AN: 68018

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00380 Hom.: 2

Bravo AF: 0.00947

Asia WGS AF: 0.0400 AC: 138 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
DANN	Benign	0.70
PhyloP100		1.4
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4252821;

hg19: chr4-77987848;