16-84604584-C-T

Variant names:

• chr16-84604584-C-T
• rs2052904
• NM_021149.5:c.160+12917G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021149.5(COTL1):​c.160+12917G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,596 control chromosomes in the GnomAD database, including 22,519 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 0.54 (22519 hom., cov: 29)
• Consequence: COTL1 NM_021149.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 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.160+12917G>A		intron	N/A	NP_066972.1	A0A384MTY2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COTL1	ENST00000262428.5	TSL:1 MANE Select	c.160+12917G>A		intron	N/A	ENSP00000262428.4	Q14019
	COTL1	ENST00000564057.1	TSL:5	c.-48+13254G>A		intron	N/A	ENSP00000457033.1	H3BT58
	COTL1	ENST00000564662.1	TSL:2	n.575+12917G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82085 AN: 151478 Hom.: 22496 Cov.: 29

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.544

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.542 AC: 82150 AN: 151596 Hom.: 22519 Cov.: 29 AF XY: 0.543 AC XY: 40191 AN XY: 74024

African (AFR) AF: 0.506 AC: 20886 AN: 41308

American (AMR) AF: 0.521 AC: 7938 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1907 AN: 3466

East Asian (EAS) AF: 0.780 AC: 3952 AN: 5064

South Asian (SAS) AF: 0.600 AC: 2886 AN: 4806

European-Finnish (FIN) AF: 0.516 AC: 5420 AN: 10508

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.547 AC: 37157 AN: 67888

Other (OTH) AF: 0.547 AC: 1151 AN: 2106

Alfa AF: 0.550 Hom.: 37470

Bravo AF: 0.541

Asia WGS AF: 0.674 AC: 2343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.51
DANN	Benign	0.61
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2052904; hg19: chr16-84638190;