Variant 6-167136580-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_031409.4(CCR6):c.350C>T(p.Thr117Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,457,164 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CCR6
NM_031409.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.901

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=0.115754664).

BP6

Variant 6-167136580-C-T is Benign according to our data. Variant chr6-167136580-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3487589.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR6	NM_031409.4 link	c.350C>T	p.Thr117Met	missense_variant	3/3	ENST00000341935.10	NP_113597.2	P51684
CCR6	NM_001394582.1 link	c.350C>T	p.Thr117Met	missense_variant	4/4		NP_001381511.1
CCR6	NM_004367.6 link	c.350C>T	p.Thr117Met	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.350C>T	p.Thr117Met	missense_variant	3/3	1	NM_031409.4	ENSP00000343952.5		P51684
ENSG00000272980	ENST00000705249.1 link	c.*303C>T		3_prime_UTR_variant	13/13			ENSP00000516101.1		A0A994J5H4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

248614

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134256

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000664

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1457164

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000699

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000831

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.11

DANN

Benign

0.63

DEOGEN2

Benign

0.053

.;T;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.099

T;T;.;.;.

M_CAP

Benign

0.0028

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.8

.;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

2.1

.;N;.;N;N

REVEL

Benign

0.036

Sift

Benign

0.58

.;T;.;T;T

Sift4G

Benign

0.41

.;T;.;T;T

Polyphen

0.0

.;B;B;B;B

Vest4

0.12, 0.12

MutPred

0.52

Loss of glycosylation at T117 (P = 0.0802);Loss of glycosylation at T117 (P = 0.0802);Loss of glycosylation at T117 (P = 0.0802);Loss of glycosylation at T117 (P = 0.0802);Loss of glycosylation at T117 (P = 0.0802);

MVP

0.22

MPC

0.61

ClinPred

0.025

GERP RS

1.2

Varity_R

0.019

gMVP

0.075

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