6-167136936-T-C

Position:

chr6-167136936-T-C

Variant summary

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

The NM_031409.4(CCR6):c.706T>C(p.Phe236Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,614,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CCR6
NM_031409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.438

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=0.061259568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR6	NM_031409.4 link	c.706T>C	p.Phe236Leu	missense_variant	3/3	ENST00000341935.10	NP_113597.2	P51684
CCR6	NM_001394582.1 link	c.706T>C	p.Phe236Leu	missense_variant	4/4		NP_001381511.1
CCR6	NM_004367.6 link	c.706T>C	p.Phe236Leu	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.706T>C	p.Phe236Leu	missense_variant	3/3	1	NM_031409.4	ENSP00000343952.5		P51684
ENSG00000272980	ENST00000705249.1 link	c.*659T>C		3_prime_UTR_variant	13/13			ENSP00000516101.1		A0A994J5H4

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000954

AC:

AN:

251478

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.000193

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000131

AC:

192

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.000165

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000112

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000147

Hom.:

Bravo

AF:

0.000110

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000474

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

Aug 01, 2024

The c.706T>C (p.F236L) alteration is located in exon 3 (coding exon 2) of the CCR6 gene. This alteration results from a T to C substitution at nucleotide position 706, causing the phenylalanine (F) at amino acid position 236 to be replaced by a leucine (L). 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

0.48

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.2

DANN

Benign

0.69

DEOGEN2

Benign

0.092

T;T;T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.60

T;.;.;.

M_CAP

Benign

0.0040

MetaRNN

Benign

0.061

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.93

L;L;L;L

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.3

N;.;N;N

REVEL

Benign

0.071

Sift

Benign

0.40

T;.;T;T

Sift4G

Benign

0.49

T;.;T;T

Polyphen

0.013

B;B;B;B

Vest4

0.043

MutPred

0.51

Gain of catalytic residue at F236 (P = 0.0763);Gain of catalytic residue at F236 (P = 0.0763);Gain of catalytic residue at F236 (P = 0.0763);Gain of catalytic residue at F236 (P = 0.0763);

MVP

0.36

MPC

0.69

ClinPred

0.043

GERP RS

2.7

Varity_R

0.12

gMVP

0.53

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over