rs151811

Positions:

• chr16-58622794-C-A
• chr16-58622794-C-G

Variant summary

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

The NM_016284.5(CNOT1):​c.-175+6934G>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 149,990 control chromosomes in the GnomAD database, including 9,980 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 (9980 hom., cov: 27)
• Consequence: CNOT1 NM_016284.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNOT1	NM_016284.5	c.-175+6934G>T		intron_variant		ENST00000317147.10	NP_057368.3
CNOT1	NM_001265612.2	c.-175+6934G>T		intron_variant			NP_001252541.1
CNOT1	NM_206999.3	c.-175+6934G>T		intron_variant			NP_996882.1
CNOT1	NR_049763.2	n.99+6934G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNOT1	ENST00000317147.10	c.-175+6934G>T		intron_variant		1	NM_016284.5	ENSP00000320949	P3

Frequencies

GnomAD3 genomes AF: 0.340 AC: 50987 AN: 149874 Hom.: 9985 Cov.: 27

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.340 AC: 50983 AN: 149990 Hom.: 9980 Cov.: 27 AF XY: 0.332 AC XY: 24304 AN XY: 73130

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.0319

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.365

Alfa AF: 0.244 Hom.: 656

Bravo AF: 0.328

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs151811; hg19: chr16-58656698;