rs154432

chr16-58626589-G-A

Variant summary

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

The NM_016284.5(CNOT1):c.-175+3139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,330 control chromosomes in the GnomAD database, including 10,118 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 0.34 (10118 hom., cov: 29)
• Consequence: CNOT1 NM_016284.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNOT1	NM_016284.5	c.-175+3139C>T		intron_variant		ENST00000317147.10
CNOT1	NM_001265612.2	c.-175+3139C>T		intron_variant
CNOT1	NM_206999.3	c.-175+3139C>T		intron_variant
CNOT1	NR_049763.2	n.99+3139C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNOT1	ENST00000317147.10	c.-175+3139C>T		intron_variant		1	NM_016284.5	P3

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51502 AN: 151212 Hom.: 10123 Cov.: 29

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.340 AC: 51497 AN: 151330 Hom.: 10118 Cov.: 29 AF XY: 0.333 AC XY: 24594 AN XY: 73910

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.0323

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.369

Alfa AF: 0.384 Hom.: 1526

Bravo AF: 0.328

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	6.5
Dann	Benign	0.80

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: rs154432; hg19: chr16-58660493;