Variant chr6-167137077-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_031409.4(CCR6):c.847A>G(p.Lys283Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.8e-7 ( 0 hom. )

Consequence

CCR6
NM_031409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.272

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:

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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=0.076789916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCR6	NM_031409.4 linkuse as main transcript	c.847A>G	p.Lys283Glu	missense_variant	3/3	ENST00000341935.10	NP_113597.2
CCR6	NM_001394582.1 linkuse as main transcript	c.847A>G	p.Lys283Glu	missense_variant	4/4		NP_001381511.1
CCR6	NM_004367.6 linkuse as main transcript	c.847A>G	p.Lys283Glu	missense_variant	3/3		NP_004358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCR6	ENST00000341935.10 linkuse as main transcript	c.847A>G	p.Lys283Glu	missense_variant	3/3	1	NM_031409.4	ENSP00000343952	P1
CCR6	ENST00000349984.6 linkuse as main transcript	c.847A>G	p.Lys283Glu	missense_variant	4/4	1		ENSP00000339393	P1
CCR6	ENST00000400926.5 linkuse as main transcript	c.847A>G	p.Lys283Glu	missense_variant	3/3	2		ENSP00000383715	P1
CCR6	ENST00000643861.1 linkuse as main transcript	c.847A>G	p.Lys283Glu	missense_variant	4/4			ENSP00000493637	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

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

May 24, 2023

The c.847A>G (p.K283E) 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 847, causing the lysine (K) at amino acid position 283 to be replaced by a glutamic acid (E). 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

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.9

DANN

Benign

0.34

DEOGEN2

Benign

0.069

T;T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.54

T;.;.;.

M_CAP

Benign

0.019

MetaRNN

Benign

0.077

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.42

N;.;N;N

REVEL

Benign

0.19

Sift

Benign

0.43

T;.;T;T

Sift4G

Benign

0.73

T;.;T;T

Polyphen

0.0020

B;B;B;B

Vest4

0.062

MutPred

0.52

Loss of ubiquitination at K283 (P = 0.0412);Loss of ubiquitination at K283 (P = 0.0412);Loss of ubiquitination at K283 (P = 0.0412);Loss of ubiquitination at K283 (P = 0.0412);

MVP

0.57

MPC

0.82

ClinPred

0.073

GERP RS

-1.4

Varity_R

0.12

gMVP

0.31

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