rs9926577

Variant names:

• chr16-58579527-C-T
• rs9926577
• NM_016284.5:c.1344-588G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016284.5(CNOT1):​c.1344-588G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,042 control chromosomes in the GnomAD database, including 43,584 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 0.75 (43584 hom., cov: 31)
• Consequence: CNOT1 NM_016284.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 11 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]

CNOT1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• holoprosencephaly 12 with or without pancreatic agenesis

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
• Vissers-Bodmer syndrome

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT1	NM_016284.5	c.1344-588G>A		intron_variant	Intron 12 of 48	ENST00000317147.10	NP_057368.3
CNOT1	NM_001265612.2	c.1344-588G>A		intron_variant	Intron 12 of 48		NP_001252541.1
CNOT1	NM_206999.3	c.1344-588G>A		intron_variant	Intron 12 of 30		NP_996882.1
CNOT1	NR_049763.2	n.1617-588G>A		intron_variant	Intron 12 of 49

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT1	ENST00000317147.10	c.1344-588G>A		intron_variant	Intron 12 of 48	1	NM_016284.5	ENSP00000320949.5

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114503 AN: 151924 Hom.: 43551 Cov.: 31

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.754 AC: 114580 AN: 152042 Hom.: 43584 Cov.: 31 AF XY: 0.748 AC XY: 55566 AN XY: 74290

African (AFR) AF: 0.841 AC: 34919 AN: 41498

American (AMR) AF: 0.651 AC: 9944 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2576 AN: 3468

East Asian (EAS) AF: 0.619 AC: 3201 AN: 5168

South Asian (SAS) AF: 0.665 AC: 3198 AN: 4810

European-Finnish (FIN) AF: 0.708 AC: 7455 AN: 10530

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50734 AN: 67986

Other (OTH) AF: 0.764 AC: 1609 AN: 2106

Alfa AF: 0.744 Hom.: 92155

Bravo AF: 0.754

Asia WGS AF: 0.647 AC: 2246 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.19
PhyloP100		-0.57
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: rs9926577; hg19: chr16-58613431;