16-84566260-A-G

Position:

• chr16-84566260-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.969

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=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COTL1	NM_021149.5	c.*585T>C		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.*585T>C		3_prime_UTR_variant	4/4	1	NM_021149.5	ENSP00000262428	P1
COTL1	ENST00000564057.1	c.*585T>C		3_prime_UTR_variant	3/3	5		ENSP00000457033
COTL1	ENST00000567278.1	n.4672T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129835 AN: 151966 Hom.: 55922 Cov.: 30

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.: 0 AF XY: 0.900 AC XY: 405 AN XY: 450

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.889

Gnomad4 FIN exome AF: 0.890

Gnomad4 NFE exome AF: 0.909

Gnomad4 OTH exome AF: 0.917

GnomAD4 genome AF: 0.854 AC: 129912 AN: 152084 Hom.: 55946 Cov.: 30 AF XY: 0.851 AC XY: 63228 AN XY: 74342

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.865

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.887

Gnomad4 FIN AF: 0.897

Gnomad4 NFE AF: 0.891

Gnomad4 OTH AF: 0.824

Alfa AF: 0.852 Hom.: 21249

Bravo AF: 0.831

Asia WGS AF: 0.792 AC: 2756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.68

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: rs247862; hg19: chr16-84599866; COSMIC: COSV52289905; COSMIC: COSV52289905;