16-84565798-A-T

Variant names:

• chr16-84565798-A-T
• rs1047121
• NM_021149.5:c.*1047T>A

Variant summary

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

The NM_021149.5(COTL1):​c.*1047T>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 0.296 in 152,300 control chromosomes in the GnomAD database, including 7,351 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 0.30 (7348 hom., cov: 34)
  • Exomes 𝑓: 0.29 (3 hom.)
• Consequence: COTL1 NM_021149.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COTL1	NM_021149.5	c.*1047T>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000262428.5	NP_066972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COTL1	ENST00000262428	c.*1047T>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_021149.5	ENSP00000262428.4
COTL1	ENST00000564057	c.*1047T>A		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000457033.1
COTL1	ENST00000567278.1	n.5134T>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45107 AN: 152116 Hom.: 7343 Cov.: 34

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.0368

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.288 AC: 19 AN: 66 Hom.: 3 Cov.: 0 AF XY: 0.273 AC XY: 12 AN XY: 44

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.296 AC: 45116 AN: 152234 Hom.: 7348 Cov.: 34 AF XY: 0.293 AC XY: 21796 AN XY: 74442

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.0369

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.295

Alfa AF: 0.227 Hom.: 561

Bravo AF: 0.280

Asia WGS AF: 0.167 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.11
DANN	Benign	0.48

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: rs1047121; hg19: chr16-84599404; COSMIC: COSV52291290; COSMIC: COSV52291290;