3-39332411-C-G

Variant names:

• chr3-39332411-C-G
• rs2853699
• NM_005201.4:c.80C>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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: 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
• Publications: 31 publications found

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]

ENSG00000287780 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005201.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR8	NM_005201.4	MANE Select	c.80C>G	p.Ala27Gly	missense	Exon 2 of 2	NP_005192.1	P51685-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR8	ENST00000326306.5	TSL:1 MANE Select	c.80C>G	p.Ala27Gly	missense	Exon 2 of 2	ENSP00000326432.4	P51685-1
	CCR8	ENST00000414803.2	TSL:1	c.80C>G	p.Ala27Gly	missense	Exon 2 of 3	ENSP00000390104.1	C9JIP9
	ENSG00000287780	ENST00000655387.2		n.435-39461G>C		intron	N/A

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

GnomAD2 exomes AF: 0.213 AC: 53478 AN: 251202 AF XY: 0.217

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 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

African (AFR) AF: 0.129 AC: 4300 AN: 33454

American (AMR) AF: 0.130 AC: 5832 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 6033 AN: 26130

East Asian (EAS) AF: 0.000705 AC: 28 AN: 39698

South Asian (SAS) AF: 0.137 AC: 11774 AN: 86252

European-Finnish (FIN) AF: 0.248 AC: 13269 AN: 53418

Middle Eastern (MID) AF: 0.204 AC: 1174 AN: 5766

European-Non Finnish (NFE) AF: 0.308 AC: 341918 AN: 1111406

Other (OTH) AF: 0.245 AC: 14780 AN: 60374

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

African (AFR) AF: 0.136 AC: 5662 AN: 41496

American (AMR) AF: 0.184 AC: 2813 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3470

East Asian (EAS) AF: 0.00308 AC: 16 AN: 5190

South Asian (SAS) AF: 0.127 AC: 610 AN: 4822

European-Finnish (FIN) AF: 0.234 AC: 2480 AN: 10584

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20983 AN: 67978

Other (OTH) AF: 0.241 AC: 510 AN: 2114

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 v4.9

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
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.92
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.0030
Sift	Benign	0.20	T
Sift4G	Benign	0.38	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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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