5-180548792-C-T

Variant names:

• chr5-180548792-C-T
• rs2453176
• NM_001370472.1:c.113-1139C>T

Variant summary

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

The NM_001370472.1(CNOT6):​c.113-1139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 152,172 control chromosomes in the GnomAD database, including 613 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 0.085 (613 hom., cov: 32)
• Consequence: CNOT6 NM_001370472.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• Publications: 19 publications found

Genes affected

CNOT6 (HGNC:14099): (CCR4-NOT transcription complex subunit 6) This gene encodes the catalytic component of the CCR4-NOT core transcriptional regulation complex. The encoded protein has a 3'-5' RNase activity and prefers polyadenylated substrates. The CCR4-NOT complex plays a role in many cellular processes, including miRNA-mediated repression, mRNA degradation, and transcriptional regulation. [provided by RefSeq, Dec 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT6	NM_001370472.1	c.113-1139C>T		intron_variant	Intron 2 of 11	ENST00000261951.9	NP_001357401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT6	ENST00000261951.9	c.113-1139C>T		intron_variant	Intron 2 of 11	5	NM_001370472.1	ENSP00000261951.4

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12895 AN: 152054 Hom.: 612 Cov.: 32

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0775

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

GnomAD4 genome AF: 0.0848 AC: 12903 AN: 152172 Hom.: 613 Cov.: 32 AF XY: 0.0823 AC XY: 6123 AN XY: 74398

African (AFR) AF: 0.0778 AC: 3228 AN: 41500

American (AMR) AF: 0.0626 AC: 956 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4820

European-Finnish (FIN) AF: 0.0959 AC: 1016 AN: 10598

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.104 AC: 7046 AN: 68010

Other (OTH) AF: 0.0767 AC: 162 AN: 2112

Alfa AF: 0.0829 Hom.: 438

Bravo AF: 0.0838

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.78
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

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: rs2453176; hg19: chr5-179975792;