Genetic Variant CCR6:c.-98+4131C>T (chr6-167127354-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031409.4(CCR6):c.-98+4131C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,942 control chromosomes in the GnomAD database, including 28,239 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 28239 hom., cov: 31)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

CCR6
NM_031409.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30

Publications

50 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCR6	NM_031409.4 link	c.-98+4131C>T	intron_variant	Intron 1 of 2	ENST00000341935.10	NP_113597.2	P51684
CCR6	NM_001394582.1 link	c.-98+4131C>T	intron_variant	Intron 2 of 3		NP_001381511.1
CCR6	NM_004367.6 link	c.-97-8684C>T	intron_variant	Intron 1 of 2		NP_004358.2	P51684
LOC107986672	XR_001744470.2 link	n.-27G>A	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR6	ENST00000341935.10 link	c.-98+4131C>T		intron_variant	Intron 1 of 2	1	NM_031409.4	ENSP00000343952.5		P51684
ENSG00000272980	ENST00000705249.1 link	c.1066-8684C>T		intron_variant	Intron 11 of 12			ENSP00000516101.1		A0A994J5H4

Frequencies

GnomAD3 genomes

AF:

0.606

AC:

92060

AN:

151818

Hom.:

28180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.689

Gnomad AMI

AF:

0.805

Gnomad AMR

AF:

0.646

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.538

Gnomad SAS

AF:

0.600

Gnomad FIN

AF:

0.546

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.561

Gnomad OTH

AF:

0.617

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.018321), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.342

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.607

AC:

92178

AN:

151936

Hom.:

28239

Cov.:

AF XY:

0.603

AC XY:

44806

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.689

AC:

28552

AN:

41444

American (AMR)

AF:

0.646

AC:

9871

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

2039

AN:

3470

East Asian (EAS)

AF:

0.538

AC:

2776

AN:

5164

South Asian (SAS)

AF:

0.602

AC:

2902

AN:

4822

European-Finnish (FIN)

AF:

0.546

AC:

5742

AN:

10522

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.561

AC:

38107

AN:

67922

Other (OTH)

AF:

0.623

AC:

1315

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1859

3718

5577

7436

9295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.581

Hom.:

42336

Bravo

AF:

0.619

Asia WGS

AF:

0.606

AC:

2103

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.014

(source)

DANN

Benign

0.23

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over