16-84604584-C-T

Position:

• chr16-84604584-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.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

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COTL1	NM_021149.5	c.160+12917G>A		intron_variant		ENST00000262428.5	NP_066972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COTL1	ENST00000262428.5	c.160+12917G>A		intron_variant		1	NM_021149.5	ENSP00000262428	P1
COTL1	ENST00000564057.1	c.-48+13254G>A		intron_variant		5		ENSP00000457033
COTL1	ENST00000564662.1	n.575+12917G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.547

Alfa AF: 0.554 Hom.: 29879

Bravo AF: 0.541

Asia WGS AF: 0.674 AC: 2343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.51
DANN	Benign	0.61

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: rs2052904; hg19: chr16-84638190;