rs151811

Variant names:

• chr16-58622794-C-A
• rs151811
• NM_016284.5:c.-175+6934G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Vissers-Bodmer syndrome

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

ACMG classification

Our verdict: Benign. The variant received -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.

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.-175+6934G>T		intron	N/A	NP_057368.3
	CNOT1	NM_001265612.2		c.-175+6934G>T		intron	N/A	NP_001252541.1	A5YKK6-2
	CNOT1	NM_206999.3		c.-175+6934G>T		intron	N/A	NP_996882.1	A5YKK6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT1	ENST00000317147.10	TSL:1 MANE Select	c.-175+6934G>T		intron	N/A	ENSP00000320949.5	A5YKK6-1
	CNOT1	ENST00000569240.5	TSL:1	c.-175+6934G>T		intron	N/A	ENSP00000455635.1	A5YKK6-2
	CNOT1	ENST00000441024.6	TSL:1	c.-175+6934G>T		intron	N/A	ENSP00000413113.2	A5YKK6-4

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

African (AFR) AF: 0.185 AC: 7561 AN: 40808

American (AMR) AF: 0.318 AC: 4784 AN: 15022

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1257 AN: 3466

East Asian (EAS) AF: 0.0319 AC: 163 AN: 5104

South Asian (SAS) AF: 0.233 AC: 1105 AN: 4744

European-Finnish (FIN) AF: 0.409 AC: 4124 AN: 10082

Middle Eastern (MID) AF: 0.362 AC: 105 AN: 290

European-Non Finnish (NFE) AF: 0.453 AC: 30581 AN: 67506

Other (OTH) AF: 0.365 AC: 756 AN: 2074

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.82
PhyloP100		0.36
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: rs151811; hg19: chr16-58656698;