rs12782946

Variant names:

• chr10-114162733-C-T
• rs12782946
• NM_018017.4:c.536G>A

Variant summary

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

The NM_018017.4(CCDC186):​c.536G>A​(p.Arg179Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0733 in 1,613,686 control chromosomes in the GnomAD database, including 4,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.057 (339 hom., cov: 33)
  • Exomes 𝑓: 0.075 (4645 hom.)
• Consequence: CCDC186 NM_018017.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428
• Publications: 17 publications found

Genes affected

CCDC186 (HGNC:24349): (coiled-coil domain containing 186) Predicted to enable small GTPase binding activity. Predicted to be involved in vesicle cytoskeletal trafficking. Predicted to act upstream of or within insulin secretion involved in cellular response to glucose stimulus and response to bacterium. Predicted to be located in Golgi apparatus. Predicted to be active in trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013920665).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018017.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC186	NM_018017.4	MANE Select	c.536G>A	p.Arg179Gln	missense	Exon 2 of 16	NP_060487.2
	CCDC186	NM_001321829.1		c.536G>A	p.Arg179Gln	missense	Exon 3 of 17	NP_001308758.1	Q7Z3E2
	CCDC186	NM_153249.1		c.536G>A	p.Arg179Gln	missense	Exon 3 of 3	NP_694981.1	Q7Z3E2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC186	ENST00000369287.8	TSL:1 MANE Select	c.536G>A	p.Arg179Gln	missense	Exon 2 of 16	ENSP00000358293.3	Q7Z3E2
	CCDC186	ENST00000369286.1	TSL:1	c.536G>A	p.Arg179Gln	missense	Exon 2 of 2	ENSP00000358292.1	A0A0C4DFU7
	CCDC186	ENST00000648613.1		c.536G>A	p.Arg179Gln	missense	Exon 3 of 17	ENSP00000498136.1	Q7Z3E2

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8689 AN: 152074 Hom.: 339 Cov.: 33

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0713

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.0672

GnomAD2 exomes AF: 0.0555 AC: 13923 AN: 251008 AF XY: 0.0552

Gnomad AFR exome AF: 0.0166

Gnomad AMR exome AF: 0.0459

Gnomad ASJ exome AF: 0.0708

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.0715

Gnomad NFE exome AF: 0.0801

Gnomad OTH exome AF: 0.0721

GnomAD4 exome AF: 0.0750 AC: 109643 AN: 1461494 Hom.: 4645 Cov.: 31 AF XY: 0.0731 AC XY: 53166 AN XY: 727040

African (AFR) AF: 0.0149 AC: 499 AN: 33470

American (AMR) AF: 0.0476 AC: 2127 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0730 AC: 1906 AN: 26118

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39668

South Asian (SAS) AF: 0.00848 AC: 731 AN: 86222

European-Finnish (FIN) AF: 0.0746 AC: 3981 AN: 53390

Middle Eastern (MID) AF: 0.0432 AC: 249 AN: 5764

European-Non Finnish (NFE) AF: 0.0864 AC: 96032 AN: 1111796

Other (OTH) AF: 0.0680 AC: 4107 AN: 60374

GnomAD4 genome AF: 0.0571 AC: 8689 AN: 152192 Hom.: 339 Cov.: 33 AF XY: 0.0559 AC XY: 4158 AN XY: 74410

African (AFR) AF: 0.0160 AC: 666 AN: 41540

American (AMR) AF: 0.0712 AC: 1088 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00766 AC: 37 AN: 4832

European-Finnish (FIN) AF: 0.0817 AC: 864 AN: 10572

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0815 AC: 5542 AN: 67996

Other (OTH) AF: 0.0665 AC: 140 AN: 2106

Alfa AF: 0.0740 Hom.: 1729

Bravo AF: 0.0562

TwinsUK AF: 0.0903 AC: 335

ALSPAC AF: 0.0929 AC: 358

ESP6500AA AF: 0.0209 AC: 92

ESP6500EA AF: 0.0826 AC: 710

ExAC AF: 0.0535 AC: 6493

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.0904

EpiControl AF: 0.0855

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.43
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.12
Sift	Benign	0.67	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.073
MPC		0.31
ClinPred		0.011	T
GERP RS		-1.3
Varity_R		0.018
gMVP		0.16
Mutation Taster		=99/1	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: rs12782946; hg19: chr10-115922492; COSMIC: COSV65159404;