rs9307306

Variant names:

• chr4-77776632-T-C
• rs9307306
• NM_144571.3:c.6-240A>G

Variant summary

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

The NM_144571.3(CNOT6L):​c.6-240A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 152,292 control chromosomes in the GnomAD database, including 500 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 0.068 (500 hom., cov: 32)
• Consequence: CNOT6L NM_144571.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 5 publications found

Genes affected

CNOT6L (HGNC:18042): (CCR4-NOT transcription complex subunit 6 like) Predicted to enable poly(A)-specific ribonuclease activity. Involved in positive regulation of cell population proliferation and positive regulation of cytoplasmic mRNA processing body assembly. Located in cytosol and nucleus. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144571.3. 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
	CNOT6L	NM_144571.3	MANE Select	c.6-240A>G		intron	N/A	NP_653172.2	Q96LI5-1
	CNOT6L	NM_001387842.1		c.189-240A>G		intron	N/A	NP_001374771.1
	CNOT6L	NM_001387843.1		c.189-240A>G		intron	N/A	NP_001374772.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT6L	ENST00000504123.7	TSL:2 MANE Select	c.6-240A>G		intron	N/A	ENSP00000424896.1	Q96LI5-1
	CNOT6L	ENST00000873612.1		c.6-240A>G		intron	N/A	ENSP00000543671.1
	CNOT6L	ENST00000512485.6	TSL:5	c.-10-240A>G		intron	N/A	ENSP00000425571.2	H0Y9Z5

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10421 AN: 152174 Hom.: 500 Cov.: 32

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0840

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

GnomAD4 genome AF: 0.0684 AC: 10418 AN: 152292 Hom.: 500 Cov.: 32 AF XY: 0.0654 AC XY: 4872 AN XY: 74480

African (AFR) AF: 0.0187 AC: 778 AN: 41576

American (AMR) AF: 0.0729 AC: 1115 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4820

European-Finnish (FIN) AF: 0.0510 AC: 541 AN: 10612

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7083 AN: 68012

Other (OTH) AF: 0.0832 AC: 176 AN: 2116

Alfa AF: 0.0945 Hom.: 1188

Bravo AF: 0.0680

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		1.6
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: rs9307306; hg19: chr4-78697786;