Variant 6-167137350-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.1120A>G(p.Met374Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 6.9e-7 ( 0 hom. )

Consequence

CCR6
NM_031409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79

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:

Genome browser will be placed here

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=0.24718145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCR6	NM_031409.4 linkuse as main transcript	c.1120A>G	p.Met374Val	missense_variant	3/3	ENST00000341935.10	NP_113597.2
CCR6	NM_001394582.1 linkuse as main transcript	c.1120A>G	p.Met374Val	missense_variant	4/4		NP_001381511.1
CCR6	NM_004367.6 linkuse as main transcript	c.1120A>G	p.Met374Val	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.1120A>G	p.Met374Val	missense_variant	3/3	1	NM_031409.4	ENSP00000343952	P1
CCR6	ENST00000349984.6 linkuse as main transcript	c.1120A>G	p.Met374Val	missense_variant	4/4	1		ENSP00000339393	P1
CCR6	ENST00000400926.5 linkuse as main transcript	c.1120A>G	p.Met374Val	missense_variant	3/3	2		ENSP00000383715	P1
CCR6	ENST00000643861.1 linkuse as main transcript	c.1120A>G	p.Met374Val	missense_variant	4/4			ENSP00000493637	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455950

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724170

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000470

Hom.:

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

Jun 10, 2022

The c.1120A>G (p.M374V) 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 1120, causing the methionine (M) at amino acid position 374 to be replaced by a valine (V). 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

0.061

BayesDel_addAF

Benign

-0.0062

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

T;T;T;T

Eigen

Benign

-0.060

Eigen_PC

Benign

0.020

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.64

T;.;.;.

M_CAP

Benign

0.022

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.0

M;M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.4

N;.;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.013

D;.;D;D

Sift4G

Uncertain

0.024

D;.;D;D

Polyphen

0.26

B;B;B;B

Vest4

0.51

MutPred

0.30

Gain of glycosylation at S371 (P = 0.1744);Gain of glycosylation at S371 (P = 0.1744);Gain of glycosylation at S371 (P = 0.1744);Gain of glycosylation at S371 (P = 0.1744);

MVP

0.62

MPC

0.62

ClinPred

0.49

GERP RS

3.7

Varity_R

0.33

gMVP

0.73

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