rs13521

Positions:

• chr16-84566364-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
COTL1	NM_021149.5	c.*481G>A		3_prime_UTR_variant	4/4	ENST00000262428.5	NP_066972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COTL1	ENST00000262428.5	c.*481G>A		3_prime_UTR_variant	4/4	1	NM_021149.5	ENSP00000262428	P1
COTL1	ENST00000564057.1	c.*481G>A		3_prime_UTR_variant	3/3	5		ENSP00000457033
COTL1	ENST00000567278.1	n.4568G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30780 AN: 151764 Hom.: 3660 Cov.: 31

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.: 23 Cov.: 0 AF XY: 0.186 AC XY: 129 AN XY: 694

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.0769

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.203 AC: 30766 AN: 151882 Hom.: 3656 Cov.: 31 AF XY: 0.199 AC XY: 14777 AN XY: 74210

Gnomad4 AFR AF: 0.0867

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.0939

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.211

Alfa AF: 0.256 Hom.: 5218

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
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs13521; hg19: chr16-84599970; COSMIC: COSV52289917; COSMIC: COSV52289917;