rs11772832

Positions:

• chr7-135388295-T-C

Variant summary

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

The ENST00000315544.6(CNOT4):​c.*499A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 981,770 control chromosomes in the GnomAD database, including 76,988 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 0.38 (10890 hom., cov: 33)
  • Exomes 𝑓: 0.40 (66098 hom.)
• Consequence: CNOT4 ENST00000315544.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708

Genes affected

CNOT4 (HGNC:7880): (CCR4-NOT transcription complex subunit 4) The protein encoded by this gene is a subunit of the CCR4-NOT complex, a global transcriptional regulator. The encoded protein interacts with CNOT1 and has E3 ubiquitin ligase activity. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (SAS) 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
CNOT4	NM_001190850.2	c.1627+5623A>G		intron_variant		ENST00000541284.6	NP_001177779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNOT4	ENST00000541284.6	c.1627+5623A>G		intron_variant		5	NM_001190850.2	ENSP00000445508	A1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57034 AN: 151974 Hom.: 10874 Cov.: 33

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.398 AC: 329844 AN: 829678 Hom.: 66098 Cov.: 28 AF XY: 0.399 AC XY: 152966 AN XY: 383194

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.434

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.457

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.375 AC: 57069 AN: 152092 Hom.: 10890 Cov.: 33 AF XY: 0.377 AC XY: 28009 AN XY: 74332

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.393

Alfa AF: 0.401 Hom.: 17476

Bravo AF: 0.377

Asia WGS AF: 0.364 AC: 1267 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11772832; hg19: chr7-135073047;