Variant 6-167136346-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031409.4(CCR6):c.116A>G(p.Gln39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCR6
NM_031409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0710

Variant links:

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]

CCR6 links:

ENSG00000272980 (HGNC:):

ENSG00000272980 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05898118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR6	NM_031409.4 link	c.116A>G	p.Gln39Arg	missense_variant	3/3	ENST00000341935.10	NP_113597.2	P51684
CCR6	NM_001394582.1 link	c.116A>G	p.Gln39Arg	missense_variant	4/4		NP_001381511.1
CCR6	NM_004367.6 link	c.116A>G	p.Gln39Arg	missense_variant	3/3		NP_004358.2	P51684

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR6	ENST00000341935.10 link	c.116A>G	p.Gln39Arg	missense_variant	3/3	1	NM_031409.4	ENSP00000343952.5		P51684
ENSG00000272980	ENST00000705249.1 link	c.*69A>G		3_prime_UTR_variant	13/13			ENSP00000516101.1		A0A994J5H4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 13, 2024

The c.116A>G (p.Q39R) alteration is located in exon 3 (coding exon 2) of the CCR6 gene. This alteration results from a A to G substitution at nucleotide position 116, causing the glutamine (Q) at amino acid position 39 to be replaced by an arginine (R). 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

0.091

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.9

DANN

Benign

0.94

DEOGEN2

Benign

0.10

.;T;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.020

T;T;.;.;.

M_CAP

Benign

0.0037

MetaRNN

Benign

0.059

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L;L;L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

.;N;.;N;N

REVEL

Benign

0.036

Sift

Benign

0.25

.;T;.;T;T

Sift4G

Benign

0.20

.;T;.;T;T

Polyphen

0.0

.;B;B;B;B

Vest4

0.031

MutPred

0.37

Gain of phosphorylation at S37 (P = 0.1924);Gain of phosphorylation at S37 (P = 0.1924);Gain of phosphorylation at S37 (P = 0.1924);Gain of phosphorylation at S37 (P = 0.1924);Gain of phosphorylation at S37 (P = 0.1924);

MVP

0.24

MPC

0.63

ClinPred

0.17

GERP RS

0.83

Varity_R

0.056

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over