rs10907376

Positions:

• chr1-223394461-G-A
• chr1-223394461-G-C
• chr1-223394461-G-T

Variant summary

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

The NM_152610.3(CCDC185):​c.986G>A​(p.Gly329Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,572,124 control chromosomes in the GnomAD database, including 52,203 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.23 (4245 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47958 hom.)
• Consequence: CCDC185 NM_152610.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.649

Genes affected

CCDC185 (HGNC:26654): (coiled-coil domain containing 185)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023890138).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC185	NM_152610.3	c.986G>A	p.Gly329Asp	missense_variant	1/1	ENST00000366875.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC185	ENST00000366875.5	c.986G>A	p.Gly329Asp	missense_variant	1/1		NM_152610.3	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35219 AN: 152022 Hom.: 4249 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.247

GnomAD3 exomes AF: 0.210 AC: 37454 AN: 178512 Hom.: 4303 AF XY: 0.210 AC XY: 20296 AN XY: 96458

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.119

Gnomad SAS exome AF: 0.126

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.233

GnomAD4 exome AF: 0.254 AC: 360089 AN: 1419982 Hom.: 47958 Cov.: 40 AF XY: 0.251 AC XY: 176183 AN XY: 702562

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.232 AC: 35242 AN: 152142 Hom.: 4245 Cov.: 32 AF XY: 0.228 AC XY: 16958 AN XY: 74364

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.245

Alfa AF: 0.257 Hom.: 9994

Bravo AF: 0.230

TwinsUK AF: 0.271 AC: 1006

ALSPAC AF: 0.276 AC: 1063

ESP6500AA AF: 0.196 AC: 834

ESP6500EA AF: 0.260 AC: 2191

ExAC AF: 0.177 AC: 20782

Asia WGS AF: 0.128 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.6
DANN	Benign	0.91
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	P
PROVEAN	Benign	0.050	N
REVEL	Benign	0.037
Sift	Benign	0.70	T
Sift4G	Benign	0.62	T
Polyphen		0.24	B
Vest4		0.020
MPC		0.47
ClinPred		0.0055	T
GERP RS		-0.73
Varity_R		0.061
gMVP		0.028

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: rs10907376; hg19: chr1-223567803; COSMIC: COSV64820791;