rs1061159

Variant names:

• chr10-114163015-G-A
• rs1061159
• NM_018017.4:c.254C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-114163015-G-A
• chr10-114163015-G-C

Variant summary

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

The NM_018017.4(CCDC186):​c.254C>T​(p.Thr85Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,613,806 control chromosomes in the GnomAD database, including 42,652 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 0.25 (5005 hom., cov: 33)
  • Exomes 𝑓: 0.22 (37647 hom.)
• Consequence: CCDC186 NM_018017.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• Publications: 25 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=0.0036338568).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC186	NM_018017.4	MANE Select	c.254C>T	p.Thr85Ile	missense	Exon 2 of 16	NP_060487.2
	CCDC186	NM_001321829.1		c.254C>T	p.Thr85Ile	missense	Exon 3 of 17	NP_001308758.1
	CCDC186	NM_153249.1		c.254C>T	p.Thr85Ile	missense	Exon 3 of 3	NP_694981.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC186	ENST00000369287.8	TSL:1 MANE Select	c.254C>T	p.Thr85Ile	missense	Exon 2 of 16	ENSP00000358293.3
	CCDC186	ENST00000369286.1	TSL:1	c.254C>T	p.Thr85Ile	missense	Exon 2 of 2	ENSP00000358292.1
	CCDC186	ENST00000648613.1		c.254C>T	p.Thr85Ile	missense	Exon 3 of 17	ENSP00000498136.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37719 AN: 152008 Hom.: 4987 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.0689

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.241

GnomAD2 exomes AF: 0.204 AC: 51311 AN: 251098 AF XY: 0.201

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.0689

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.230

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.223 AC: 325317 AN: 1461680 Hom.: 37647 Cov.: 34 AF XY: 0.220 AC XY: 159781 AN XY: 727128

African (AFR) AF: 0.324 AC: 10841 AN: 33470

American (AMR) AF: 0.169 AC: 7552 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 8370 AN: 26120

East Asian (EAS) AF: 0.0678 AC: 2690 AN: 39686

South Asian (SAS) AF: 0.140 AC: 12056 AN: 86222

European-Finnish (FIN) AF: 0.205 AC: 10927 AN: 53390

Middle Eastern (MID) AF: 0.284 AC: 1636 AN: 5768

European-Non Finnish (NFE) AF: 0.231 AC: 257197 AN: 1111924

Other (OTH) AF: 0.233 AC: 14048 AN: 60390

GnomAD4 genome AF: 0.248 AC: 37786 AN: 152126 Hom.: 5005 Cov.: 33 AF XY: 0.245 AC XY: 18203 AN XY: 74380

African (AFR) AF: 0.326 AC: 13533 AN: 41486

American (AMR) AF: 0.221 AC: 3384 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1112 AN: 3472

East Asian (EAS) AF: 0.0692 AC: 359 AN: 5186

South Asian (SAS) AF: 0.127 AC: 615 AN: 4828

European-Finnish (FIN) AF: 0.200 AC: 2116 AN: 10588

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15760 AN: 67972

Other (OTH) AF: 0.242 AC: 512 AN: 2114

Alfa AF: 0.235 Hom.: 15115

Bravo AF: 0.254

TwinsUK AF: 0.225 AC: 836

ALSPAC AF: 0.244 AC: 941

ESP6500AA AF: 0.317 AC: 1395

ESP6500EA AF: 0.235 AC: 2024

ExAC AF: 0.206 AC: 24995

Asia WGS AF: 0.137 AC: 478 AN: 3478

EpiCase AF: 0.247

EpiControl AF: 0.237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.072
DANN	Benign	0.17
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.68
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.15
Sift	Benign	0.42	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.027
MPC		0.29
ClinPred		0.0080	T
GERP RS		-9.5
Varity_R		0.024
gMVP		0.063
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1061159; hg19: chr10-115922774; COSMIC: COSV65159408;