1-223394461-G-A

Variant names:

• chr1-223394461-G-A
• rs10907376
• NM_152610.3:c.986G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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 0.23 (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
• Publications: 20 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152610.3. 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
	CCDC185	NM_152610.3	MANE Select	c.986G>A	p.Gly329Asp	missense	Exon 1 of 1	NP_689823.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC185	ENST00000366875.5	TSL:6 MANE Select	c.986G>A	p.Gly329Asp	missense	Exon 1 of 1	ENSP00000355840.3

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

GnomAD2 exomes AF: 0.210 AC: 37454 AN: 178512 AF XY: 0.210

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 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

African (AFR) AF: 0.194 AC: 6325 AN: 32560

American (AMR) AF: 0.149 AC: 5637 AN: 37792

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4731 AN: 25466

East Asian (EAS) AF: 0.115 AC: 4307 AN: 37456

South Asian (SAS) AF: 0.125 AC: 10141 AN: 81428

European-Finnish (FIN) AF: 0.250 AC: 12306 AN: 49208

Middle Eastern (MID) AF: 0.268 AC: 1527 AN: 5696

European-Non Finnish (NFE) AF: 0.276 AC: 300991 AN: 1091510

Other (OTH) AF: 0.240 AC: 14124 AN: 58866

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

African (AFR) AF: 0.201 AC: 8363 AN: 41526

American (AMR) AF: 0.207 AC: 3158 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 637 AN: 3472

East Asian (EAS) AF: 0.116 AC: 599 AN: 5152

South Asian (SAS) AF: 0.123 AC: 591 AN: 4824

European-Finnish (FIN) AF: 0.229 AC: 2419 AN: 10576

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18554 AN: 67984

Other (OTH) AF: 0.245 AC: 519 AN: 2116

Alfa AF: 0.254 Hom.: 16138

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 v4.9

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
PhyloP100		0.65
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
Mutation Taster		=100/0	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: rs10907376; hg19: chr1-223567803; COSMIC: COSV64820791;