chr6-167137336-C-T

Position:

chr6-167137336-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_031409.4(CCR6):c.1106C>T(p.Ala369Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00763 in 1,612,360 control chromosomes in the GnomAD database, including 64 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0079 ( 61 hom. )

Consequence

CCR6
NM_031409.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.212

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004140228).

BP6

Variant 6-167137336-C-T is Benign according to our data. Variant chr6-167137336-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 709155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCR6	NM_031409.4 linkuse as main transcript	c.1106C>T	p.Ala369Val	missense_variant	3/3	ENST00000341935.10	NP_113597.2
CCR6	NM_001394582.1 linkuse as main transcript	c.1106C>T	p.Ala369Val	missense_variant	4/4		NP_001381511.1
CCR6	NM_004367.6 linkuse as main transcript	c.1106C>T	p.Ala369Val	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.1106C>T	p.Ala369Val	missense_variant	3/3	1	NM_031409.4	ENSP00000343952	P1
CCR6	ENST00000349984.6 linkuse as main transcript	c.1106C>T	p.Ala369Val	missense_variant	4/4	1		ENSP00000339393	P1
CCR6	ENST00000400926.5 linkuse as main transcript	c.1106C>T	p.Ala369Val	missense_variant	3/3	2		ENSP00000383715	P1
CCR6	ENST00000643861.1 linkuse as main transcript	c.1106C>T	p.Ala369Val	missense_variant	4/4			ENSP00000493637	P1

Frequencies

GnomAD3 genomes

AF:

0.00458

AC:

697

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00859

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00701

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00532

AC:

1331

AN:

250016

Hom.:

AF XY:

0.00528

AC XY:

714

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.00442

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000494

Gnomad FIN exome

AF:

0.00928

Gnomad NFE exome

AF:

0.00853

Gnomad OTH exome

AF:

0.00657

GnomAD4 exome

AF:

0.00794

AC:

11600

AN:

1460122

Hom.:

Cov.:

AF XY:

0.00763

AC XY:

5540

AN XY:

726376

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00419

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000569

Gnomad4 FIN exome

AF:

0.0103

Gnomad4 NFE exome

AF:

0.00938

Gnomad4 OTH exome

AF:

0.00614

GnomAD4 genome

AF:

0.00458

AC:

697

AN:

152238

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

301

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00859

Gnomad4 NFE

AF:

0.00701

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00648

Hom.:

Bravo

AF:

0.00420

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00930

AC:

ExAC

AF:

0.00543

AC:

659

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00671

EpiControl

AF:

0.00682

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	CCR6: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.0

DANN

Benign

0.97

DEOGEN2

Benign

0.089

T;T;T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.65

T;.;.;.

M_CAP

Benign

0.026

MetaRNN

Benign

0.0041

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

N;.;N;N

REVEL

Benign

0.054

Sift

Benign

0.073

T;.;T;T

Sift4G

Benign

0.15

T;.;T;T

Polyphen

0.051

B;B;B;B

Vest4

0.022

MVP

0.76

MPC

0.59

ClinPred

0.0026

GERP RS

2.1

Varity_R

0.040

gMVP

0.42

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