5-132747849-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001039780.4(CCNI2):​c.354C>T​(p.Asp118Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000272 in 1,472,472 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CCNI2 NM_001039780.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.

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>T	p.Asp118Asp	synonymous	Exon 1 of 6	NP_001034869.1	Q6ZMN8-1
	CCNI2	NM_001287252.2		c.354C>T	p.Asp118Asp	synonymous	Exon 1 of 6	NP_001274181.1	Q6ZMN8-2
	CCNI2	NM_001287253.2		c.354C>T	p.Asp118Asp	synonymous	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>T	p.Asp118Asp	synonymous	Exon 1 of 6	ENSP00000368005.1	Q6ZMN8-1
	CCNI2	ENST00000614847.1	TSL:1	c.354C>T	p.Asp118Asp	synonymous	Exon 1 of 6	ENSP00000478257.1	Q6ZMN8-2
	CCNI2	ENST00000878149.1		c.354C>T	p.Asp118Asp	synonymous	Exon 1 of 6	ENSP00000548208.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000268 AC: 2 AN: 74494 AF XY: 0.0000466

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000688

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000224

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000227 AC: 3 AN: 1320252 Hom.: 0 Cov.: 31 AF XY: 0.00000308 AC XY: 2 AN XY: 650228

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.0000773 AC: 2 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: 71836

European-Finnish (FIN) AF: 0.0000305 AC: 1 AN: 32766

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051480

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000647710), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74364

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.3
DANN	Benign	0.88
PhyloP100		-1.9
PromoterAI		-0.011	Neutral

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;