rs854685

Positions:

• chr17-35992090-C-T

Variant summary

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

The ENST00000616694.1(CCL15-CCL14):​n.*47-5386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,014 control chromosomes in the GnomAD database, including 3,368 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 0.19 (3368 hom., cov: 32)
• Consequence: CCL15-CCL14 ENST00000616694.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926

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-CCL14 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL15-CCL14	NR_027921.3	n.935-5386G>A		intron_variant
CCL15-CCL14	NR_027922.3	n.935-5386G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL15-CCL14	ENST00000616694.1	n.*47-5386G>A		intron_variant		2		ENSP00000481402.1
CCL15-CCL14	ENST00000610751.4	n.*47-5386G>A		intron_variant		2		ENSP00000481940.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29217 AN: 151894 Hom.: 3355 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.193 AC: 29275 AN: 152014 Hom.: 3368 Cov.: 32 AF XY: 0.194 AC XY: 14425 AN XY: 74334

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0959

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.164

Alfa AF: 0.143 Hom.: 2237

Bravo AF: 0.195

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.35
DANN	Benign	0.31

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: rs854685; hg19: chr17-34319126;