rs37062

chr16-58533334-A-G

Variant summary

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

The NM_016284.5(CNOT1):c.5895+813T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,826 control chromosomes in the GnomAD database, including 4,876 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 0.24 (4876 hom., cov: 32)
• Consequence: CNOT1 NM_016284.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNOT1	NM_016284.5	c.5895+813T>C		intron_variant		ENST00000317147.10
CNOT1	NM_001265612.2	c.5880+813T>C		intron_variant
CNOT1	NR_049763.2	n.6153+813T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNOT1	ENST00000317147.10	c.5895+813T>C		intron_variant		1	NM_016284.5	P3
CNOT1	ENST00000569240.5	c.5880+813T>C		intron_variant		1		A1
CNOT1	ENST00000567188.5	c.5880+813T>C		intron_variant, NMD_transcript_variant		1
CNOT1	ENST00000568917.1	c.1035+813T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36858 AN: 151708 Hom.: 4861 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.243 AC: 36899 AN: 151826 Hom.: 4876 Cov.: 32 AF XY: 0.247 AC XY: 18343 AN XY: 74214

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.236

Alfa AF: 0.254 Hom.: 848

Bravo AF: 0.245

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	6.5
Dann	Benign	0.57

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: rs37062; hg19: chr16-58567238;