Genetic Variant CCR4:p.Tyr338Tyr (chr3-32954436-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005508.5(CCR4):c.1014C>T(p.Tyr338Tyr) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0290

Publications

35 publications found

Variant links:

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]

CCR4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCR4	NM_005508.5 link	c.1014C>T	p.Tyr338Tyr	synonymous_variant	Exon 2 of 2	ENST00000330953.6	NP_005499.1	P51679A0N0Q1
CCR4	XM_017005687.2 link	c.1014C>T	p.Tyr338Tyr	synonymous_variant	Exon 2 of 2		XP_016861176.1	P51679A0N0Q1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR4	ENST00000330953.6 link	c.1014C>T	p.Tyr338Tyr	synonymous_variant	Exon 2 of 2	1	NM_005508.5	ENSP00000332659.5		P51679
CCR4	ENST00000718415.1 link	c.1014C>T	p.Tyr338Tyr	synonymous_variant	Exon 2 of 2			ENSP00000520802.1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34198

AN:

152010

Hom.:

4785

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.250

AC:

57649

AN:

230446

AF XY:

0.255

show subpopulations

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 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.:

AF XY:

0.285

AC XY:

204133

AN XY:

715400

show subpopulations

African (AFR)

AF:

0.0684

AC:

2227

AN:

32558

American (AMR)

AF:

0.261

AC:

10687

AN:

41020

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

6969

AN:

24510

East Asian (EAS)

AF:

0.0248

AC:

982

AN:

39632

South Asian (SAS)

AF:

0.201

AC:

16408

AN:

81598

European-Finnish (FIN)

AF:

0.260

AC:

13678

AN:

52696

Middle Eastern (MID)

AF:

0.354

AC:

1993

AN:

5630

European-Non Finnish (NFE)

AF:

0.311

AC:

343690

AN:

1103358

Other (OTH)

AF:

0.264

AC:

15681

AN:

59480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14979

29957

44936

59914

74893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10984

21968

32952

43936

54920

<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:

0.225

AC:

34199

AN:

152130

Hom.:

4790

Cov.:

AF XY:

0.220

AC XY:

16369

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0769

AC:

3195

AN:

41524

American (AMR)

AF:

0.264

AC:

4033

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1035

AN:

3472

East Asian (EAS)

AF:

0.0214

AC:

111

AN:

5184

South Asian (SAS)

AF:

0.188

AC:

907

AN:

4824

European-Finnish (FIN)

AF:

0.248

AC:

2626

AN:

10568

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.313

AC:

21267

AN:

67970

Other (OTH)

AF:

0.246

AC:

519

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1275

2551

3826

5102

6377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

356

712

1068

1424

1780

<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:

0.274

Hom.:

8717

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

(source)

DANN

Benign

0.30

PhyloP100

0.029

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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