chr4-77385265-A-G

Variant names:

• chr4-77385265-A-G
• rs9307270
• ENST00000497512.5:n.1676-46975A>G

Variant summary

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

The ENST00000497512.5(CCNG2):​n.1676-46975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 152,240 control chromosomes in the GnomAD database, including 658 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 0.087 (658 hom., cov: 32)
• Consequence: CCNG2 ENST00000497512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 3 publications found

Genes affected

CCNG2 (HGNC:1593): (cyclin G2) The eukaryotic cell cycle is governed by cyclin-dependent protein kinases (CDKs) whose activities are regulated by cyclins and CDK inhibitors. The 8 species of cyclins reported in mammals, cyclins A through H, share a conserved amino acid sequence of about 90 residues called the cyclin box. The amino acid sequence of cyclin G is well conserved among mammals. The nucleotide sequence of cyclin G1 and cyclin G2 are 53% identical. Unlike cyclin G1, cyclin G2 contains a C-terminal PEST protein destabilization motif, suggesting that cyclin G2 expression is tightly regulated through the cell cycle. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNG2	ENST00000497512.5	n.1676-46975A>G		intron_variant	Intron 10 of 11	1
CCNG2	ENST00000514756.1	n.232+498A>G		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0873 AC: 13273 AN: 152122 Hom.: 659 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0721

Gnomad ASJ AF: 0.0858

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.0872 AC: 13271 AN: 152240 Hom.: 658 Cov.: 32 AF XY: 0.0906 AC XY: 6746 AN XY: 74424

African (AFR) AF: 0.0566 AC: 2350 AN: 41548

American (AMR) AF: 0.0722 AC: 1105 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0858 AC: 298 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1021 AN: 5164

South Asian (SAS) AF: 0.165 AC: 794 AN: 4816

European-Finnish (FIN) AF: 0.109 AC: 1153 AN: 10614

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0917 AC: 6238 AN: 68008

Other (OTH) AF: 0.0900 AC: 190 AN: 2112

Alfa AF: 0.0942 Hom.: 459

Bravo AF: 0.0829

Asia WGS AF: 0.162 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.4
DANN	Benign	0.74
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9307270; hg19: chr4-78306419;