chr10-114135200-C-G

Position:

• chr10-114135200-C-G

Variant summary

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

The ENST00000369287.8(CCDC186):​c.1513-145G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 785,710 control chromosomes in the GnomAD database, including 135,689 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 0.65 (33847 hom., cov: 31)
  • Exomes 𝑓: 0.56 (101842 hom.)
• Consequence: CCDC186 ENST00000369287.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC186	NM_018017.4	c.1513-145G>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.1513-145G>C		intron_variant		1	NM_018017.4	ENSP00000358293	P1
CCDC186	ENST00000428953.1	c.398-145G>C		intron_variant		2		ENSP00000415344
CCDC186	ENST00000648613.1	c.1513-145G>C		intron_variant				ENSP00000498136	P1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98267 AN: 151834 Hom.: 33782 Cov.: 31

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.590

GnomAD4 exome AF: 0.559 AC: 354070 AN: 633758 Hom.: 101842 AF XY: 0.558 AC XY: 178147 AN XY: 319048

Gnomad4 AFR exome AF: 0.912

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.540

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.583

Gnomad4 FIN exome AF: 0.532

Gnomad4 NFE exome AF: 0.559

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.648 AC: 98390 AN: 151952 Hom.: 33847 Cov.: 31 AF XY: 0.640 AC XY: 47512 AN XY: 74278

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.591

Alfa AF: 0.471 Hom.: 1248

Bravo AF: 0.660

Asia WGS AF: 0.558 AC: 1935 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.55
DANN	Benign	0.26

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: rs7902873; hg19: chr10-115894959;