Variant chr3-32954407-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005508.5(CCR4):c.985T>G(p.Cys329Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,457,434 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CCR4
NM_005508.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR4	NM_005508.5 linkuse as main transcript	c.985T>G	p.Cys329Gly	missense_variant	2/2	ENST00000330953.6
CCR4	XM_017005687.2 linkuse as main transcript	c.985T>G	p.Cys329Gly	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR4	ENST00000330953.6 linkuse as main transcript	c.985T>G	p.Cys329Gly	missense_variant	2/2	1	NM_005508.5	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000446

AC:

AN:

246594

Hom.:

AF XY:

0.0000675

AC XY:

AN XY:

133390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000339

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000804

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1457434

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

724910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.985T>G (p.C329G) alteration is located in exon 2 (coding exon 1) of the CCR4 gene. This alteration results from a T to G substitution at nucleotide position 985, causing the cysteine (C) at amino acid position 329 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.0081

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.54

M_CAP

Benign

0.063

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.51

Sift

Benign

0.098

Sift4G

Benign

0.16

Polyphen

0.93

Vest4

0.54

MutPred

0.61

Gain of relative solvent accessibility (P = 0.0479);

MVP

0.78

MPC

0.64

ClinPred

0.77

GERP RS

4.1

Varity_R

0.21

gMVP

0.73

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over