3-39332411-C-G

Position:

• chr3-39332411-C-G

Variant summary

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

The NM_005201.4(CCR8):​c.80C>G​(p.Ala27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,350 control chromosomes in the GnomAD database, including 63,851 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.23 (4529 hom., cov: 32)
  • Exomes 𝑓: 0.27 (59322 hom.)
• Consequence: CCR8 NM_005201.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915

Genes affected

CCR8 (HGNC:1609): (C-C motif chemokine receptor 8) This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptors are important for the migration of various cell types into the inflammatory sites. This receptor protein preferentially expresses in the thymus. I-309, thymus activation-regulated cytokine (TARC) and macrophage inflammatory protein-1 beta (MIP-1 beta) have been identified as ligands of this receptor. Studies of this receptor and its ligands suggested its role in regulation of monocyte chemotaxis and thymic cell apoptosis. More specifically, this receptor may contribute to the proper positioning of activated T cells within the antigenic challenge sites and specialized areas of lymphoid tissues. This gene is located at the chemokine receptor gene cluster region. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00552842).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR8	NM_005201.4	c.80C>G	p.Ala27Gly	missense_variant	2/2	ENST00000326306.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR8	ENST00000326306.5	c.80C>G	p.Ala27Gly	missense_variant	2/2	1	NM_005201.4	P1
CCR8	ENST00000414803.1	c.80C>G	p.Ala27Gly	missense_variant	2/3	1
	ENST00000655387.1	n.370-39461G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34284 AN: 152016 Hom.: 4528 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.213 AC: 53478 AN: 251202 Hom.: 7029 AF XY: 0.217 AC XY: 29424 AN XY: 135752

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.122

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.000761

Gnomad SAS exome AF: 0.135

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.300

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.273 AC: 399108 AN: 1461216 Hom.: 59322 Cov.: 35 AF XY: 0.270 AC XY: 196300 AN XY: 726960

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.000705

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.225 AC: 34290 AN: 152134 Hom.: 4529 Cov.: 32 AF XY: 0.218 AC XY: 16190 AN XY: 74384

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.241

Alfa AF: 0.266 Hom.: 4423

Bravo AF: 0.218

TwinsUK AF: 0.311 AC: 1154

ALSPAC AF: 0.298 AC: 1149

ESP6500AA AF: 0.144 AC: 635

ESP6500EA AF: 0.304 AC: 2611

ExAC AF: 0.215 AC: 26152

Asia WGS AF: 0.0600 AC: 209 AN: 3478

EpiCase AF: 0.305

EpiControl AF: 0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.13
DANN	Benign	0.60
DEOGEN2	Benign	0.052	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.16	T;T
MetaRNN	Benign	0.0055	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.010	N;N
REVEL	Benign	0.0030
Sift	Benign	0.20	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.0	B;.
Vest4		0.044
MPC		0.10
ClinPred		0.00058	T
GERP RS		-3.2
Varity_R		0.033
gMVP		0.051

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: rs2853699; hg19: chr3-39373902; COSMIC: COSV58336969; COSMIC: COSV58336969;