rs2061634

chr9-97343500-C-Gchr9-97343500-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020893.6(CCDC180):c.2435C>G(p.Ser812Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,612,734 control chromosomes in the GnomAD database, including 58,719 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7274 hom., cov: 32)
  • Exomes 𝑓: 0.26 (51445 hom.)
• Consequence: CCDC180 NM_020893.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.620

Genes affected

CCDC180 (HGNC:29303): (coiled-coil domain containing 180) The protein encoded by this gene contains a coiled-coil domain. Alternative splicing results in multiple transcript variants encoding different isoforms. A single nucleotide polymorphism (SNP) in this gene has been associated with increased susceptibility to Behcet's Disease (PMID: 19442274). [provided by RefSeq, Dec 2016]

SUGT1P4-STRA6LP-CCDC180 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012887716).
• BP6: Variant 9-97343500-C-G is Benign according to our data. Variant chr9-97343500-C-G is described in ClinVar as [Benign]. Clinvar id is 1268803.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC180	NM_020893.6	c.2435C>G	p.Ser812Cys	missense_variant	19/37	ENST00000529487.3
SUGT1P4-STRA6LP-CCDC180	NR_036528.1	n.3990C>G		non_coding_transcript_exon_variant	33/51

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC180	ENST00000529487.3	c.2435C>G	p.Ser812Cys	missense_variant	19/37	1	NM_020893.6	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44827 AN: 151876 Hom.: 7265 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.290

GnomAD3 exomes AF: 0.266 AC: 66801 AN: 251382 Hom.: 9567 AF XY: 0.265 AC XY: 35965 AN XY: 135874

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.185

Gnomad SAS exome AF: 0.279

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.261 AC: 381048 AN: 1460740 Hom.: 51445 Cov.: 35 AF XY: 0.262 AC XY: 190058 AN XY: 726740

Gnomad4 AFR exome AF: 0.420

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.295 AC: 44876 AN: 151994 Hom.: 7274 Cov.: 32 AF XY: 0.288 AC XY: 21388 AN XY: 74308

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.289

Alfa AF: 0.265 Hom.: 4203

Bravo AF: 0.312

TwinsUK AF: 0.257 AC: 952

ALSPAC AF: 0.255 AC: 982

ESP6500AA AF: 0.419 AC: 1846

ESP6500EA AF: 0.273 AC: 2349

ExAC AF: 0.269 AC: 32615

Asia WGS AF: 0.216 AC: 750 AN: 3478

EpiCase AF: 0.276

EpiControl AF: 0.271

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 17, 2020

This variant is associated with the following publications: (PMID: 19442274) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	14
Dann	Benign	0.96
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.038
Sift	Benign	0.088	T
Sift4G	Uncertain	0.0070	D
Vest4		0.099
ClinPred		0.0079	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.051

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: rs2061634; hg19: chr9-100105782; COSMIC: COSV63830627;