rs2904524

Positions:

• chr12-70296305-G-A
• chr12-70296305-G-C
• chr12-70296305-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014515.7(CNOT2):​c.49-14590G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,094 control chromosomes in the GnomAD database, including 2,155 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 0.16 (2155 hom., cov: 31)
• Consequence: CNOT2 NM_014515.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157

Genes affected

CNOT2 (HGNC:7878): (CCR4-NOT transcription complex subunit 2) This gene encodes a subunit of the multi-component CCR4-NOT complex. The CCR4-NOT complex regulates mRNA synthesis and degradation and is also thought to be involved in mRNA splicing, transport and localization. The encoded protein interacts with histone deacetylases and functions as a repressor of polymerase II transcription. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNOT2	NM_014515.7	c.49-14590G>A		intron_variant		ENST00000229195.8	NP_055330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNOT2	ENST00000229195.8	c.49-14590G>A		intron_variant		1	NM_014515.7	ENSP00000229195.3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23936 AN: 151976 Hom.: 2151 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.158 AC: 23979 AN: 152094 Hom.: 2155 Cov.: 31 AF XY: 0.161 AC XY: 12005 AN XY: 74340

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.171

Alfa AF: 0.120 Hom.: 761

Bravo AF: 0.166

Asia WGS AF: 0.267 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs2904524; hg19: chr12-70690085;