rs368254487

Variant names:

• chr17-36001480-C-A
• rs368254487
• NM_032965.6:c.13G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-36001480-C-A
• chr17-36001480-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032965.6(CCL15):​c.13G>T​(p.Val5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCL15 NM_032965.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732

Genes affected

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]

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]

ENSG00000275944 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0455333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL15	NM_032965.6	c.13G>T	p.Val5Leu	missense_variant	Exon 1 of 4	ENST00000617897.2	NP_116741.2
CCL15-CCL14	NR_027921.3	n.559G>T		non_coding_transcript_exon_variant	Exon 1 of 8
CCL15-CCL14	NR_027922.3	n.559G>T		non_coding_transcript_exon_variant	Exon 1 of 7
LOC107985068	XR_001752854.2	n.-49C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL15	ENST00000617897.2	c.13G>T	p.Val5Leu	missense_variant	Exon 1 of 4	1	NM_032965.6	ENSP00000484078.1
CCL15-CCL14	ENST00000616694.1	n.13G>T		non_coding_transcript_exon_variant	Exon 1 of 7	2		ENSP00000481402.1
CCL15-CCL14	ENST00000610751.4	n.13G>T		non_coding_transcript_exon_variant	Exon 1 of 8	2		ENSP00000481940.1
ENSG00000275944	ENST00000619334.1	n.62C>A		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.40
DANN	Benign	0.56
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.24	T
Sift4G	Benign	0.28	T
Vest4		0.072
MutPred		0.32		Loss of ubiquitination at K2 (P = 0.1306);
MVP		0.28
ClinPred		0.19	T
GERP RS		-4.9
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs368254487; hg19: chr17-34328519;