6-167136700-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031409.4(CCR6):c.470G>A(p.Arg157Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: CCR6 NM_031409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.83

Genes affected

CCR6 (HGNC:1607): (C-C motif chemokine receptor 6) This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. The gene is preferentially expressed by immature dendritic cells and memory T cells. The ligand of this receptor is macrophage inflammatory protein 3 alpha (MIP-3 alpha). This receptor has been shown to be important for B-lineage maturation and antigen-driven B-cell differentiation, and it may regulate the migration and recruitment of dentritic and T cells during inflammatory and immunological responses. Alternatively spliced transcript variants that encode the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR6	NM_031409.4	c.470G>A	p.Arg157Gln	missense_variant	3/3	ENST00000341935.10
CCR6	NM_001394582.1	c.470G>A	p.Arg157Gln	missense_variant	4/4
CCR6	NM_004367.6	c.470G>A	p.Arg157Gln	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR6	ENST00000341935.10	c.470G>A	p.Arg157Gln	missense_variant	3/3	1	NM_031409.4	P1
CCR6	ENST00000349984.6	c.470G>A	p.Arg157Gln	missense_variant	4/4	1		P1
CCR6	ENST00000400926.5	c.470G>A	p.Arg157Gln	missense_variant	3/3	2		P1
CCR6	ENST00000643861.1	c.470G>A	p.Arg157Gln	missense_variant	4/4			P1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

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: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251288 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135852

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461808 Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152318 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74466

Gnomad4 AFR AF: 0.0000481

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: 0.0000294

Gnomad4 OTH AF: 0.000473

Bravo AF: 0.0000151

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.470G>A (p.R157Q) alteration is located in exon 3 (coding exon 2) of the CCR6 gene. This alteration results from a G to A substitution at nucleotide position 470, causing the arginine (R) at amino acid position 157 to be replaced by a glutamine (Q). 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	0.19
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Uncertain	-0.040
Cadd	Uncertain	24
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.19	T;T;T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;.;.;.
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.89	D;D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.3	M;M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	N;.;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.070	T;.;T;T
Sift4G	Benign	0.065	T;.;T;T
Polyphen		0.89	P;P;P;P
Vest4		0.59
MutPred		0.77		Loss of methylation at R157 (P = 0.0159);Loss of methylation at R157 (P = 0.0159);Loss of methylation at R157 (P = 0.0159);Loss of methylation at R157 (P = 0.0159);
MVP		0.86
MPC		1.4
ClinPred		0.94	D
GERP RS		4.9
Varity_R		0.47
gMVP		0.80

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: rs566661955; hg19: chr6-167550188; COSMIC: COSV59474365; COSMIC: COSV59474365;