rs7188697

Positions:

• chr16-58588274-G-A
• chr16-58588274-G-C

Variant summary

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

The NM_016284.5(CNOT1):​c.211-396C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 151,958 control chromosomes in the GnomAD database, including 43,414 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 (43414 hom., cov: 31)
• Consequence: CNOT1 NM_016284.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

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=-0.97).
• 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/exons	MANE	Protein	UniProt
CNOT1	NM_016284.5	c.211-396C>T		intron_variant		ENST00000317147.10	NP_057368.3
CNOT1	NM_001265612.2	c.211-396C>T		intron_variant			NP_001252541.1
CNOT1	NM_206999.3	c.211-396C>T		intron_variant			NP_996882.1
CNOT1	NR_049763.2	n.484-396C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNOT1	ENST00000317147.10	c.211-396C>T		intron_variant		1	NM_016284.5	ENSP00000320949	P3

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114241 AN: 151840 Hom.: 43381 Cov.: 31

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.752 AC: 114318 AN: 151958 Hom.: 43414 Cov.: 31 AF XY: 0.747 AC XY: 55460 AN XY: 74268

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.763

Alfa AF: 0.739 Hom.: 28541

Bravo AF: 0.753

Asia WGS AF: 0.647 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.37
DANN	Benign	0.81

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: rs7188697; hg19: chr16-58622178;