Genetic Variant NM_144571.3:c.*3094A>G (chr4-77717337-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144571.3(CNOT6L):c.*3094A>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 0.789 in 152,378 control chromosomes in the GnomAD database, including 48,254 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 0.79 ( 48098 hom., cov: 31)

Exomes 𝑓: 0.84 ( 156 hom. )

Consequence

CNOT6L
NM_144571.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.328

Publications

9 publications found

Variant links:

Genes affected

CNOT6L (HGNC:18042): (CCR4-NOT transcription complex subunit 6 like) Predicted to enable poly(A)-specific ribonuclease activity. Involved in positive regulation of cell population proliferation and positive regulation of cytoplasmic mRNA processing body assembly. Located in cytosol and nucleus. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

CNOT6L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT6L	NM_144571.3 link	c.*3094A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000504123.7	NP_653172.2	Q96LI5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT6L	ENST00000504123.7 link	c.*3094A>G		3_prime_UTR_variant	Exon 12 of 12	2	NM_144571.3	ENSP00000424896.1		Q96LI5-1
CNOT6L	ENST00000649644.1 link	c.*3094A>G		3_prime_UTR_variant	Exon 12 of 12			ENSP00000497467.1		H0Y9Z5

Frequencies

GnomAD3 genomes

AF:

0.789

AC:

119743

AN:

151822

Hom.:

48071

Cov.:

show subpopulations

Gnomad AFR

AF:

0.628

Gnomad AMI

AF:

0.851

Gnomad AMR

AF:

0.852

Gnomad ASJ

AF:

0.873

Gnomad EAS

AF:

0.823

Gnomad SAS

AF:

0.756

Gnomad FIN

AF:

0.825

Gnomad MID

AF:

0.732

Gnomad NFE

AF:

0.860

Gnomad OTH

AF:

0.823

GnomAD4 exome

AF:

0.845

AC:

370

AN:

438

Hom.:

156

Cov.:

AF XY:

0.845

AC XY:

223

AN XY:

264

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.844

AC:

363

AN:

430

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.789

AC:

119811

AN:

151940

Hom.:

48098

Cov.:

AF XY:

0.786

AC XY:

58398

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.628

AC:

25999

AN:

41404

American (AMR)

AF:

0.852

AC:

12986

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.873

AC:

3028

AN:

3470

East Asian (EAS)

AF:

0.823

AC:

4248

AN:

5162

South Asian (SAS)

AF:

0.756

AC:

3643

AN:

4816

European-Finnish (FIN)

AF:

0.825

AC:

8718

AN:

10568

Middle Eastern (MID)

AF:

0.733

AC:

214

AN:

292

European-Non Finnish (NFE)

AF:

0.860

AC:

58465

AN:

67968

Other (OTH)

AF:

0.822

AC:

1734

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1196

2391

3587

4782

5978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.839

Hom.:

64446

Bravo

AF:

0.784

Asia WGS

AF:

0.753

AC:

2620

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over