5-180553302-T-A

Variant names:

• chr5-180553302-T-A
• rs10516143
• NM_001370472.1:c.300-84T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.79).
• 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 rank	MANE	Protein	UniProt
CNOT6	NM_001370472.1	c.300-84T>A		intron_variant	Intron 3 of 11	ENST00000261951.9	NP_001357401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT6	ENST00000261951.9	c.300-84T>A		intron_variant	Intron 3 of 11	5	NM_001370472.1	ENSP00000261951.4

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

African (AFR) AF: 0.285 AC: 5078 AN: 17810

American (AMR) AF: 0.386 AC: 11292 AN: 29258

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 11255 AN: 18796

East Asian (EAS) AF: 0.198 AC: 6871 AN: 34740

South Asian (SAS) AF: 0.451 AC: 27633 AN: 61236

European-Finnish (FIN) AF: 0.491 AC: 23710 AN: 48322

Middle Eastern (MID) AF: 0.522 AC: 2155 AN: 4132

European-Non Finnish (NFE) AF: 0.524 AC: 242714 AN: 463100

Other (OTH) AF: 0.480 AC: 16768 AN: 34914

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

African (AFR) AF: 0.286 AC: 11858 AN: 41444

American (AMR) AF: 0.421 AC: 6435 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2076 AN: 3464

East Asian (EAS) AF: 0.231 AC: 1196 AN: 5172

South Asian (SAS) AF: 0.433 AC: 2081 AN: 4808

European-Finnish (FIN) AF: 0.494 AC: 5205 AN: 10528

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36382 AN: 67934

Other (OTH) AF: 0.439 AC: 927 AN: 2114

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
PhyloP100		0.47
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: rs10516143; hg19: chr5-179980302; COSMIC: COSV56160388; COSMIC: COSV56160388;