rs10946216

Variant names:

• chr6-167125409-T-C
• rs10946216
• NM_031409.4:c.-98+2186T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031409.4(CCR6):​c.-98+2186T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,138 control chromosomes in the GnomAD database, including 28,520 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 (28520 hom., cov: 33)
• Consequence: CCR6 NM_031409.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 15 publications found

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]

ENSG00000272980 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR6	NM_031409.4	c.-98+2186T>C		intron_variant	Intron 1 of 2	ENST00000341935.10	NP_113597.2
CCR6	NM_001394582.1	c.-98+2186T>C		intron_variant	Intron 2 of 3		NP_001381511.1
CCR6	NM_004367.6	c.-97-10629T>C		intron_variant	Intron 1 of 2		NP_004358.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR6	ENST00000341935.10	c.-98+2186T>C		intron_variant	Intron 1 of 2	1	NM_031409.4	ENSP00000343952.5
ENSG00000272980	ENST00000705249.1	c.1066-10629T>C		intron_variant	Intron 11 of 12			ENSP00000516101.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92560 AN: 152018 Hom.: 28462 Cov.: 33

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.619

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.609 AC: 92677 AN: 152138 Hom.: 28520 Cov.: 33 AF XY: 0.606 AC XY: 45038 AN XY: 74364

African (AFR) AF: 0.689 AC: 28604 AN: 41494

American (AMR) AF: 0.650 AC: 9943 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2042 AN: 3472

East Asian (EAS) AF: 0.540 AC: 2800 AN: 5184

South Asian (SAS) AF: 0.603 AC: 2909 AN: 4828

European-Finnish (FIN) AF: 0.546 AC: 5784 AN: 10584

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38405 AN: 67972

Other (OTH) AF: 0.624 AC: 1320 AN: 2114

Alfa AF: 0.592 Hom.: 3337

Bravo AF: 0.621

Asia WGS AF: 0.611 AC: 2120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.70
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10946216; hg19: chr6-167538897; COSMIC: COSV59476027; COSMIC: COSV59476027;