4-77734118-T-C

Position:

• chr4-77734118-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.873-2580A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,088 control chromosomes in the GnomAD database, including 48,141 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 0.79 (48141 hom., cov: 32)
• Consequence: CNOT6L NM_144571.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNOT6L	NM_144571.3	c.873-2580A>G		intron_variant		ENST00000504123.7	NP_653172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNOT6L	ENST00000504123.7	c.873-2580A>G		intron_variant		2	NM_144571.3	ENSP00000424896.1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119865 AN: 151970 Hom.: 48107 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.789 AC: 119950 AN: 152088 Hom.: 48141 Cov.: 32 AF XY: 0.786 AC XY: 58447 AN XY: 74328

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.860

Gnomad4 OTH AF: 0.827

Alfa AF: 0.820 Hom.: 7781

Bravo AF: 0.785

Asia WGS AF: 0.767 AC: 2670 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.83

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: rs7674744; hg19: chr4-78655272;