6-167137336-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0079 (61 hom.)
• Consequence: CCR6 NM_031409.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.212

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]

ACMG classification

Verdict is Benign. Variant got -10 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 [Benign]. Clinvar id is 709155.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR6	NM_031409.4	c.1106C>T	p.Ala369Val	missense_variant	3/3	ENST00000341935.10
CCR6	NM_001394582.1	c.1106C>T	p.Ala369Val	missense_variant	4/4
CCR6	NM_004367.6	c.1106C>T	p.Ala369Val	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR6	ENST00000341935.10	c.1106C>T	p.Ala369Val	missense_variant	3/3	1	NM_031409.4	P1
CCR6	ENST00000349984.6	c.1106C>T	p.Ala369Val	missense_variant	4/4	1		P1
CCR6	ENST00000400926.5	c.1106C>T	p.Ala369Val	missense_variant	3/3	2		P1
CCR6	ENST00000643861.1	c.1106C>T	p.Ala369Val	missense_variant	4/4			P1

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 697 AN: 152120 Hom.: 3 Cov.: 33

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.: 3 AF XY: 0.00528 AC XY: 714 AN XY: 135174

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.: 61 Cov.: 33 AF XY: 0.00763 AC XY: 5540 AN XY: 726376

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.: 3 Cov.: 33 AF XY: 0.00404 AC XY: 301 AN XY: 74434

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.: 5

Bravo AF: 0.00420

TwinsUK AF: 0.0108 AC: 40

ALSPAC AF: 0.00830 AC: 32

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00930 AC: 80

ExAC AF: 0.00543 AC: 659

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00671

EpiControl AF: 0.00682

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.55	T
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	N
LIST_S2	Benign	0.65	T;.;.;.
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.0041	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;L;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.30	T
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	T
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

Other links and lift over

dbSNP: rs17860852; hg19: chr6-167550824; COSMIC: COSV59474374; COSMIC: COSV59474374;