rs10509999

Positions:

• chr10-114167520-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369287.8(CCDC186):​c.-61-4191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 152,066 control chromosomes in the GnomAD database, including 672 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 0.086 (672 hom., cov: 29)
• Consequence: CCDC186 ENST00000369287.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC186	NM_018017.4	c.-61-4191T>C		intron_variant		ENST00000369287.8	NP_060487.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC186	ENST00000369287.8	c.-61-4191T>C		intron_variant		1	NM_018017.4	ENSP00000358293	P1
CCDC186	ENST00000369286.1	c.-61-4191T>C		intron_variant		1		ENSP00000358292
CCDC186	ENST00000369285.7	c.-61-4191T>C		intron_variant		2		ENSP00000358291
CCDC186	ENST00000648613.1	c.-61-4191T>C		intron_variant				ENSP00000498136	P1

Frequencies

GnomAD3 genomes AF: 0.0857 AC: 13020 AN: 151948 Hom.: 666 Cov.: 29

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0952

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0857 AC: 13039 AN: 152066 Hom.: 672 Cov.: 29 AF XY: 0.0836 AC XY: 6217 AN XY: 74338

Gnomad4 AFR AF: 0.0598

Gnomad4 AMR AF: 0.0940

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0248

Gnomad4 FIN AF: 0.0952

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0946 Hom.: 256

Bravo AF: 0.0867

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.1
DANN	Benign	0.39

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: rs10509999; hg19: chr10-115927279;