Genetic Variant COTL1:c.*585T>C (chr16-84566260-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021149.5(COTL1):c.*585T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,084 control chromosomes in the GnomAD database, including 55,946 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 0.85 ( 55946 hom., cov: 30)

Exomes 𝑓: 0.89 ( 281 hom. )

Failed GnomAD Quality Control

Consequence

COTL1
NM_021149.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.969

Publications

9 publications found

Variant links:

Genes affected

COTL1 (HGNC:18304): (coactosin like F-actin binding protein 1) This gene encodes one of the numerous actin-binding proteins which regulate the actin cytoskeleton. This protein binds F-actin, and also interacts with 5-lipoxygenase, which is the first committed enzyme in leukotriene biosynthesis. Although this gene has been reported to map to chromosome 17 in the Smith-Magenis syndrome region, the best alignments for this gene are to chromosome 16. The Smith-Magenis syndrome region is the site of two related pseudogenes. [provided by RefSeq, Jul 2008]

COTL1 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=-0.59).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021149.5. 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
	COTL1	NM_021149.5	MANE Select	c.*585T>C		3_prime_UTR	Exon 4 of 4	NP_066972.1	A0A384MTY2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COTL1	ENST00000262428.5	TSL:1 MANE Select	c.*585T>C	3_prime_UTR	Exon 4 of 4	ENSP00000262428.4	Q14019
COTL1	ENST00000564057.1	TSL:5	c.*585T>C	3_prime_UTR	Exon 3 of 3	ENSP00000457033.1	H3BT58
COTL1	ENST00000567278.1	TSL:2	n.4672T>C	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.854

AC:

129835

AN:

151966

Hom.:

55922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.861

Gnomad AMI

AF:

0.849

Gnomad AMR

AF:

0.664

Gnomad ASJ

AF:

0.865

Gnomad EAS

AF:

0.770

Gnomad SAS

AF:

0.887

Gnomad FIN

AF:

0.897

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.891

Gnomad OTH

AF:

0.825

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.895

AC:

621

AN:

694

Hom.:

281

Cov.:

AF XY:

0.900

AC XY:

405

AN XY:

450

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.889

AC:

AN:

European-Finnish (FIN)

AF:

0.890

AC:

390

AN:

438

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.909

AC:

180

AN:

198

Other (OTH)

AF:

0.917

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.854

AC:

129912

AN:

152084

Hom.:

55946

Cov.:

AF XY:

0.851

AC XY:

63228

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.861

AC:

35699

AN:

41472

American (AMR)

AF:

0.663

AC:

10131

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.865

AC:

3001

AN:

3470

East Asian (EAS)

AF:

0.770

AC:

3974

AN:

5162

South Asian (SAS)

AF:

0.887

AC:

4274

AN:

4816

European-Finnish (FIN)

AF:

0.897

AC:

9512

AN:

10604

Middle Eastern (MID)

AF:

0.820

AC:

241

AN:

294

European-Non Finnish (NFE)

AF:

0.891

AC:

60571

AN:

67976

Other (OTH)

AF:

0.824

AC:

1736

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

943

1885

2828

3770

4713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.852

Hom.:

25444

Bravo

AF:

0.831

Asia WGS

AF:

0.792

AC:

2756

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

0.97

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over