Genetic Variant COTL1:c.*1047T>A (chr16-84565798-A-T) – 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.*1047T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,300 control chromosomes in the GnomAD database, including 7,351 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 0.30 ( 7348 hom., cov: 34)

Exomes 𝑓: 0.29 ( 3 hom. )

Consequence

COTL1
NM_021149.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.98

Publications

7 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:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COTL1	NM_021149.5	MANE Select	c.*1047T>A		3_prime_UTR	Exon 4 of 4	NP_066972.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
COTL1	ENST00000262428.5	TSL:1 MANE Select	c.*1047T>A	3_prime_UTR	Exon 4 of 4	ENSP00000262428.4
COTL1	ENST00000567278.1	TSL:2	n.5134T>A	non_coding_transcript_exon	Exon 2 of 2
COTL1	ENST00000564057.1	TSL:5	c.*1047T>A	3_prime_UTR	Exon 3 of 3	ENSP00000457033.1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45107

AN:

152116

Hom.:

7343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.0368

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.297

GnomAD4 exome

AF:

0.288

AC:

AN:

Hom.:

Cov.:

AF XY:

0.273

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.295

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.214

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.296

AC:

45116

AN:

152234

Hom.:

7348

Cov.:

AF XY:

0.293

AC XY:

21796

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.206

AC:

8575

AN:

41558

American (AMR)

AF:

0.220

AC:

3370

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

1275

AN:

3472

East Asian (EAS)

AF:

0.0369

AC:

191

AN:

5180

South Asian (SAS)

AF:

0.353

AC:

1703

AN:

4824

European-Finnish (FIN)

AF:

0.342

AC:

3627

AN:

10600

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.375

AC:

25462

AN:

67988

Other (OTH)

AF:

0.295

AC:

622

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1635

3270

4905

6540

8175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.227

Hom.:

561

Bravo

AF:

0.280

Asia WGS

AF:

0.167

AC:

586

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.11

(source)

DANN

Benign

0.48

PhyloP100

-2.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over