chr3-32954094-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005508.5(CCR4):​c.672G>T​(p.Met224Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

CCR4
NM_005508.5 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.98
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1278567).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCR4NM_005508.5 linkuse as main transcriptc.672G>T p.Met224Ile missense_variant 2/2 ENST00000330953.6
CCR4XM_017005687.2 linkuse as main transcriptc.672G>T p.Met224Ile missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCR4ENST00000330953.6 linkuse as main transcriptc.672G>T p.Met224Ile missense_variant 2/21 NM_005508.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251308
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135820
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461852
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152280
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsJul 06, 2022The c.672G>T (p.M224I) alteration is located in exon 2 (coding exon 1) of the CCR4 gene. This alteration results from a G to T substitution at nucleotide position 672, causing the methionine (M) at amino acid position 224 to be replaced by an isoleucine (I). 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
Uncertain
0.44
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.14
Eigen_PC
Benign
0.062
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.0099
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.60
N
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.084
Sift
Uncertain
0.0080
D
Sift4G
Benign
0.086
T
Polyphen
0.0070
B
Vest4
0.36
MutPred
0.61
Gain of catalytic residue at L229 (P = 0.0667);
MVP
0.39
MPC
0.25
ClinPred
0.31
T
GERP RS
5.1
Varity_R
0.32
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs181979629; hg19: chr3-32995586; API