chr3-32954407-T-G

Variant summary

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

The NM_005508.5(CCR4):ā€‹c.985T>Gā€‹(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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000023 ( 0 hom. )

Consequence

CCR4
NM_005508.5 missense

Scores

1
9
9

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]

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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
CCR4NM_005508.5 linkuse as main transcriptc.985T>G p.Cys329Gly missense_variant 2/2 ENST00000330953.6
CCR4XM_017005687.2 linkuse as main transcriptc.985T>G p.Cys329Gly missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCR4ENST00000330953.6 linkuse as main transcriptc.985T>G p.Cys329Gly missense_variant 2/21 NM_005508.5 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000446
AC:
11
AN:
246594
Hom.:
0
AF XY:
0.0000675
AC XY:
9
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:
33
AN:
1457434
Hom.:
0
Cov.:
32
AF XY:
0.0000276
AC XY:
20
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.:
32
ExAC
AF:
0.0000577
AC:
7

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 submitterclinical testingAmbry GeneticsJan 24, 2024The 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
T
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.37
T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.063
D
MetaRNN
Uncertain
0.66
D
MetaSVM
Benign
-0.65
T
MutationAssessor
Uncertain
2.4
M
MutationTaster
Benign
0.99
D
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-2.8
D
REVEL
Uncertain
0.51
Sift
Benign
0.098
T
Sift4G
Benign
0.16
T
Polyphen
0.93
P
Vest4
0.54
MutPred
0.61
Gain of relative solvent accessibility (P = 0.0479);
MVP
0.78
MPC
0.64
ClinPred
0.77
D
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.

Other links and lift over

dbSNP: rs774861204; hg19: chr3-32995899; API