rs2228428

Positions:

• chr3-32954436-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005508.5(CCR4):​c.1014C>T​(p.Tyr338=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,592,612 control chromosomes in the GnomAD database, including 67,171 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 0.22 (4790 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62381 hom.)
• Consequence: CCR4 NM_005508.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

Genes affected

CCR4 (HGNC:1605): (C-C motif chemokine receptor 4) The protein encoded by this gene belongs to the G-protein-coupled receptor family . It is a receptor for the CC chemokine - MIP-1, RANTES, TARC and MCP-1. Chemokines are a group of small polypeptide, structurally related molecules that regulate cell trafficking of various types of leukocytes. The chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.029 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR4	NM_005508.5	c.1014C>T	p.Tyr338=	synonymous_variant	2/2	ENST00000330953.6
CCR4	XM_017005687.2	c.1014C>T	p.Tyr338=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR4	ENST00000330953.6	c.1014C>T	p.Tyr338=	synonymous_variant	2/2	1	NM_005508.5	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34198 AN: 152010 Hom.: 4785 Cov.: 32

Gnomad AFR AF: 0.0772

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.249

GnomAD3 exomes AF: 0.250 AC: 57649 AN: 230446 Hom.: 8300 AF XY: 0.255 AC XY: 31695 AN XY: 124110

Gnomad AFR exome AF: 0.0690

Gnomad AMR exome AF: 0.261

Gnomad ASJ exome AF: 0.293

Gnomad EAS exome AF: 0.0146

Gnomad SAS exome AF: 0.202

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.319

Gnomad OTH exome AF: 0.275

GnomAD4 exome AF: 0.286 AC: 412315 AN: 1440482 Hom.: 62381 Cov.: 34 AF XY: 0.285 AC XY: 204133 AN XY: 715400

Gnomad4 AFR exome AF: 0.0684

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.0248

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.225 AC: 34199 AN: 152130 Hom.: 4790 Cov.: 32 AF XY: 0.220 AC XY: 16369 AN XY: 74364

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.246

Alfa AF: 0.277 Hom.: 6084

Bravo AF: 0.217

Asia WGS AF: 0.101 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
DANN	Benign	0.30

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: rs2228428; hg19: chr3-32995928; COSMIC: COSV58384363;