16-58520876-C-T

Variant names:

• chr16-58520876-C-T
• rs17821549
• NM_016284.5:c.*82G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_016284.5(CNOT1):​c.*82G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 1,416,214 control chromosomes in the GnomAD database, including 3,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (263 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3126 hom.)
• Consequence: CNOT1 NM_016284.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.52
• Publications: 4 publications found

Genes affected

CNOT1 (HGNC:7877): (CCR4-NOT transcription complex subunit 1) Enables armadillo repeat domain binding activity; molecular adaptor activity; and nuclear receptor binding activity. Contributes to poly(A)-specific ribonuclease activity. Involved in several processes, including negative regulation of signal transduction; positive regulation of cytoplasmic mRNA processing body assembly; and regulation of gene expression. Located in P-body and cytosol. Part of CCR4-NOT complex. Implicated in holoprosencephaly. [provided by Alliance of Genome Resources, Apr 2022]

SETD6 (HGNC:26116): (SET domain containing 6, protein lysine methyltransferase) This gene encodes a methyltransferase that adds a methyl group to the histone H2AZ, which is involved in nuclear receptor-dependent transcription. The protein also interacts with several endogenous proteins which are involved in nuclear hormone receptor signaling. A related pseudogene is located on chromosome 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

SETD6 Gene-Disease associations (from GenCC):

• colorectal cancer

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 16-58520876-C-T is Benign according to our data. Variant chr16-58520876-C-T is described in ClinVar as Benign. ClinVar VariationId is 1289270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016284.5. 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
	CNOT1	NM_016284.5	MANE Select	c.*82G>A		3_prime_UTR	Exon 49 of 49	NP_057368.3
	SETD6	NM_001160305.4	MANE Select	c.*1847C>T		3_prime_UTR	Exon 8 of 8	NP_001153777.1	Q8TBK2-1
	CNOT1	NM_001265612.2		c.*82G>A		3_prime_UTR	Exon 49 of 49	NP_001252541.1	A5YKK6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT1	ENST00000317147.10	TSL:1 MANE Select	c.*82G>A		3_prime_UTR	Exon 49 of 49	ENSP00000320949.5	A5YKK6-1
	SETD6	ENST00000219315.9	TSL:1 MANE Select	c.*1847C>T		3_prime_UTR	Exon 8 of 8	ENSP00000219315.5	Q8TBK2-1
	CNOT1	ENST00000569240.5	TSL:1	c.*82G>A		3_prime_UTR	Exon 49 of 49	ENSP00000455635.1	A5YKK6-2

Frequencies

GnomAD3 genomes AF: 0.0503 AC: 7653 AN: 152180 Hom.: 263 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0876

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0769

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0707

Gnomad OTH AF: 0.0636

GnomAD4 exome AF: 0.0658 AC: 83106 AN: 1263916 Hom.: 3126 Cov.: 18 AF XY: 0.0668 AC XY: 42568 AN XY: 636944

African (AFR) AF: 0.0112 AC: 334 AN: 29802

American (AMR) AF: 0.0397 AC: 1752 AN: 44138

Ashkenazi Jewish (ASJ) AF: 0.0932 AC: 2284 AN: 24506

East Asian (EAS) AF: 0.000206 AC: 8 AN: 38780

South Asian (SAS) AF: 0.0864 AC: 7061 AN: 81708

European-Finnish (FIN) AF: 0.0634 AC: 2560 AN: 40360

Middle Eastern (MID) AF: 0.104 AC: 550 AN: 5310

European-Non Finnish (NFE) AF: 0.0687 AC: 64905 AN: 945382

Other (OTH) AF: 0.0677 AC: 3652 AN: 53930

GnomAD4 genome AF: 0.0502 AC: 7650 AN: 152298 Hom.: 263 Cov.: 32 AF XY: 0.0503 AC XY: 3747 AN XY: 74462

African (AFR) AF: 0.0126 AC: 524 AN: 41566

American (AMR) AF: 0.0480 AC: 734 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0876 AC: 304 AN: 3470

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.0769 AC: 371 AN: 4822

European-Finnish (FIN) AF: 0.0655 AC: 695 AN: 10614

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0707 AC: 4808 AN: 68016

Other (OTH) AF: 0.0630 AC: 133 AN: 2112

Alfa AF: 0.0604 Hom.: 131

Bravo AF: 0.0458

Asia WGS AF: 0.0260 AC: 89 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17821549; hg19: chr16-58554780; COSMIC: COSV54700103; COSMIC: COSV54700103;