chr19-54154264-G-C

Position:

• chr19-54154264-G-C

Variant summary

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

The ENST00000221232.11(CNOT3):​c.2163+424G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 345,074 control chromosomes in the GnomAD database, including 56,313 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 0.59 (28317 hom., cov: 32)
  • Exomes 𝑓: 0.53 (27996 hom.)
• Consequence: CNOT3 ENST00000221232.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

Genes affected

CNOT3 (HGNC:7879): (CCR4-NOT transcription complex subunit 3) Involved in regulation of stem cell population maintenance. Part of CCR4-NOT complex. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNOT3	NM_014516.4	c.2163+424G>C		intron_variant		ENST00000221232.11	NP_055331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNOT3	ENST00000221232.11	c.2163+424G>C		intron_variant		1	NM_014516.4	ENSP00000221232	P1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89971 AN: 151940 Hom.: 28280 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.528 AC: 101866 AN: 193016 Hom.: 27996 Cov.: 0 AF XY: 0.539 AC XY: 56078 AN XY: 104024

Gnomad4 AFR exome AF: 0.802

Gnomad4 AMR exome AF: 0.635

Gnomad4 ASJ exome AF: 0.609

Gnomad4 EAS exome AF: 0.642

Gnomad4 SAS exome AF: 0.631

Gnomad4 FIN exome AF: 0.475

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.592 AC: 90064 AN: 152058 Hom.: 28317 Cov.: 32 AF XY: 0.597 AC XY: 44342 AN XY: 74306

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.578

Alfa AF: 0.353 Hom.: 789

Bravo AF: 0.610

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1055234; hg19: chr19-54658001;