ENST00000616694.1:n.*46+813G>A

Variant names:

• chr17-35996908-C-T
• rs854692
• ENST00000616694.1:n.*46+813G>A

Variant summary

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

The ENST00000616694.1(CCL15-CCL14):​n.*46+813G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,100 control chromosomes in the GnomAD database, including 17,227 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 0.40 (17225 hom., cov: 32)
  • Exomes 𝑓: 0.23 (2 hom.)
• Consequence: CCL15-CCL14 ENST00000616694.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 9 publications found

Genes affected

CCL15-CCL14 (HGNC:44436): (CCL15-CCL14 readthrough (NMD candidate)) A cluster of CC chemokine genes exists on chromosome 17q11.2. The CC chemokines are secreted proteins characterized by two adjacent cysteines. The genes chemokine (C-C motif) ligand 14 and chemokine (C-C motif) ligand 15 are adjacent loci and express read-through transcripts spanning both loci. The read-through transcripts were originally interpreted as bicistronic transcripts, but they are represented as non-coding because they are candidates for nonsense-mediated mRNA decay (NMD). [provided by RefSeq, Dec 2009]

CCL15 (HGNC:10613): (C-C motif chemokine ligand 15) This gene is located in a cluster of similar genes in the same region of chromosome 17. These genes encode CC cytokines, which are secreted proteins characterized by two adjacent cysteines. The product of this gene is chemotactic for T cells and monocytes, and acts through C-C chemokine receptor type 1 (CCR1). The proprotein is further processed into numerous smaller functional peptides. Naturally-occurring readthrough transcripts occur from this gene into the downstream gene, CCL14 (chemokine (C-C motif) ligand 14). [provided by RefSeq, Jan 2013]

ENSG00000270240 (HGNC:58767):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000616694.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL15-CCL14	NR_027921.3		n.934+813G>A		intron	N/A
	CCL15-CCL14	NR_027922.3		n.934+813G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL15-CCL14	ENST00000616694.1	TSL:2	n.*46+813G>A		intron	N/A	ENSP00000481402.1
	CCL15	ENST00000614368.1	TSL:3	c.*65G>A		3_prime_UTR	Exon 3 of 3	ENSP00000484262.1
	CCL15-CCL14	ENST00000610751.4	TSL:2	n.*46+813G>A		intron	N/A	ENSP00000481940.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60664 AN: 151892 Hom.: 17179 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.233 AC: 21 AN: 90 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 19 AN XY: 76

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.205 AC: 16 AN: 78

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.400 AC: 60762 AN: 152010 Hom.: 17225 Cov.: 32 AF XY: 0.402 AC XY: 29885 AN XY: 74274

African (AFR) AF: 0.804 AC: 33302 AN: 41442

American (AMR) AF: 0.313 AC: 4780 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 764 AN: 3472

East Asian (EAS) AF: 0.467 AC: 2412 AN: 5164

South Asian (SAS) AF: 0.405 AC: 1948 AN: 4812

European-Finnish (FIN) AF: 0.232 AC: 2448 AN: 10572

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14009 AN: 67972

Other (OTH) AF: 0.337 AC: 712 AN: 2114

Alfa AF: 0.273 Hom.: 23756

Bravo AF: 0.417

Asia WGS AF: 0.458 AC: 1591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.1
DANN	Benign	0.79
PhyloP100		-0.067
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs854692; hg19: chr17-34323944;