rs10516143

Positions:

• chr5-180553302-T-A
• chr5-180553302-T-C

Variant summary

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

The NM_001370472.1(CNOT6):​c.300-84T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 864,250 control chromosomes in the GnomAD database, including 103,743 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 0.44 (15649 hom., cov: 31)
  • Exomes 𝑓: 0.49 (88094 hom.)
• Consequence: CNOT6 NM_001370472.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNOT6	NM_001370472.1	c.300-84T>A		intron_variant		ENST00000261951.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNOT6	ENST00000261951.9	c.300-84T>A		intron_variant		5	NM_001370472.1	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66669 AN: 151824 Hom.: 15648 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.488 AC: 347476 AN: 712308 Hom.: 88094 AF XY: 0.490 AC XY: 184499 AN XY: 376554

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.386

Gnomad4 ASJ exome AF: 0.599

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.491

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.480

GnomAD4 genome AF: 0.439 AC: 66681 AN: 151942 Hom.: 15649 Cov.: 31 AF XY: 0.438 AC XY: 32545 AN XY: 74268

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.439

Alfa AF: 0.476 Hom.: 2127

Bravo AF: 0.424

Asia WGS AF: 0.296 AC: 1030 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.5
DANN	Benign	0.46

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: rs10516143; hg19: chr5-179980302; COSMIC: COSV56160388; COSMIC: COSV56160388;