dbSNP rs13521: COTL1:c.*481G>A (chr16-84566364-C-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.*481G>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 0.203 in 153,158 control chromosomes in the GnomAD database, including 3,679 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 0.20 ( 3656 hom., cov: 31)

Exomes 𝑓: 0.20 ( 23 hom. )

Consequence

COTL1
NM_021149.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.154

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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COTL1	NM_021149.5 link	c.*481G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000262428.5	NP_066972.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
COTL1	ENST00000262428.5 link	c.*481G>A	3_prime_UTR_variant	Exon 4 of 4	1	NM_021149.5	ENSP00000262428.4
COTL1	ENST00000567278.1 link	n.4568G>A	non_coding_transcript_exon_variant	Exon 2 of 2	2
COTL1	ENST00000564057.1 link	c.*481G>A	3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000457033.1
COTL1	ENST00000561707.1 link	n.*186G>A	downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30780

AN:

151764

Hom.:

3660

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0870

Gnomad AMI

AF:

0.303

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.0941

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.214

GnomAD4 exome

AF:

0.199

AC:

254

AN:

1276

Hom.:

Cov.:

AF XY:

0.186

AC XY:

129

AN XY:

694

show subpopulations

African (AFR)

AF:

0.0714

AC:

AN:

American (AMR)

AF:

0.104

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.286

AC:

AN:

South Asian (SAS)

AF:

0.0769

AC:

AN:

182

European-Finnish (FIN)

AF:

0.196

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.227

AC:

203

AN:

894

Other (OTH)

AF:

0.220

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.203

AC:

30766

AN:

151882

Hom.:

3656

Cov.:

AF XY:

0.199

AC XY:

14777

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.0867

AC:

3592

AN:

41440

American (AMR)

AF:

0.186

AC:

2847

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

558

AN:

3462

East Asian (EAS)

AF:

0.192

AC:

986

AN:

5138

South Asian (SAS)

AF:

0.0939

AC:

452

AN:

4812

European-Finnish (FIN)

AF:

0.250

AC:

2631

AN:

10536

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18945

AN:

67910

Other (OTH)

AF:

0.211

AC:

446

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1190

2379

3569

4758

5948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.248

Hom.:

13063

Bravo

AF:

0.195

Asia WGS

AF:

0.154

AC:

535

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.8

(source)

DANN

Benign

0.68

PhyloP100

0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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