Variant rs1133763 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005623.3(CCL8):c.205A>C(p.Lys69Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,601,202 control chromosomes in the GnomAD database, including 27,316 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2210 hom., cov: 32)

Exomes 𝑓: 0.17 ( 25106 hom. )

Consequence

CCL8
NM_005623.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

CCL8 (HGNC:10635): (C-C motif chemokine ligand 8) This antimicrobial gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes, lymphocytes, basophils and eosinophils. By recruiting leukocytes to sites of inflammation this cytokine may contribute to tumor-associated leukocyte infiltration and to the antiviral state against HIV infection. [provided by RefSeq, Sep 2014]

CCL8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001110673).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL8	NM_005623.3 linkuse as main transcript	c.205A>C	p.Lys69Gln	missense_variant	3/3	ENST00000394620.2	NP_005614.2	P80075

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL8	ENST00000394620.2 linkuse as main transcript	c.205A>C	p.Lys69Gln	missense_variant	3/3	1	NM_005623.3	ENSP00000378118.1		P80075

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22940

AN:

152050

Hom.:

2201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0639

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.155

GnomAD3 exomes

AF:

0.207

AC:

50140

AN:

242118

Hom.:

6348

AF XY:

0.210

AC XY:

27624

AN XY:

131232

show subpopulations

Gnomad AFR exome

AF:

0.0620

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.314

Gnomad SAS exome

AF:

0.360

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.174

AC:

252455

AN:

1449034

Hom.:

25106

Cov.:

AF XY:

0.180

AC XY:

129455

AN XY:

721154

show subpopulations

Gnomad4 AFR exome

AF:

0.0606

Gnomad4 AMR exome

AF:

0.309

Gnomad4 ASJ exome

AF:

0.158

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.155

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.151

AC:

22980

AN:

152168

Hom.:

2210

Cov.:

AF XY:

0.157

AC XY:

11684

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0640

Gnomad4 AMR

AF:

0.248

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.368

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.161

Alfa

AF:

0.163

Hom.:

2801

Bravo

AF:

0.152

TwinsUK

AF:

0.164

AC:

607

ALSPAC

AF:

0.155

AC:

596

ESP6500AA

AF:

0.0722

AC:

318

ESP6500EA

AF:

0.161

AC:

1384

ExAC

AF:

0.204

AC:

24805

Asia WGS

AF:

0.301

AC:

1046

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0011

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.34

REVEL

Benign

0.061

Sift4G

Benign

0.085

Polyphen

0.87

Vest4

0.088

MPC

0.57

ClinPred

0.045

GERP RS

3.1

Varity_R

0.24

gMVP

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over