dbSNP rs854692: CCL15-CCL14:n.*46+813G>A (chr17-35996908-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0670

Publications

9 publications found

Variant links:

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 links:

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 links:

ENSG00000270240 (HGNC:58767):

ENSG00000270240 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL15-CCL14	NR_027921.3 link	n.934+813G>A		intron_variant	Intron 4 of 7
CCL15-CCL14	NR_027922.3 link	n.934+813G>A		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
CCL15-CCL14	ENST00000616694.1 link	n.*46+813G>A	intron_variant	Intron 4 of 6	2	ENSP00000481402.1
CCL15	ENST00000614368.1 link	c.*65G>A	3_prime_UTR_variant	Exon 3 of 3	3	ENSP00000484262.1
CCL15-CCL14	ENST00000610751.4 link	n.*46+813G>A	intron_variant	Intron 4 of 7	2	ENSP00000481940.1
ENSG00000270240	ENST00000788510.1 link	n.149-291C>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60664

AN:

151892

Hom.:

17179

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.205

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.400

AC:

60762

AN:

152010

Hom.:

17225

Cov.:

AF XY:

0.402

AC XY:

29885

AN XY:

74274

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

14009

AN:

67972

Other (OTH)

AF:

0.337

AC:

712

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1313

2626

3940

5253

6566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

510

1020

1530

2040

2550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.1

(source)

DANN

Benign

0.79

PhyloP100

-0.067

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over