rs9307306

chr4-77776632-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNOT6L	NM_144571.3	c.6-240A>G		intron_variant		ENST00000504123.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNOT6L	ENST00000504123.7	c.6-240A>G		intron_variant		2	NM_144571.3

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

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.0729

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0510

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0832

Alfa AF: 0.0973 Hom.: 970

Bravo AF: 0.0680

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	12
Dann	Benign	0.80

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: rs9307306; hg19: chr4-78697786;