9-97376879-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020893.6(CCDC180):c.4959A>G(p.Gln1653=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,610,386 control chromosomes in the GnomAD database, including 56,767 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 0.33 (9989 hom., cov: 32)
  • Exomes 𝑓: 0.23 (46778 hom.)
• Consequence: CCDC180 NM_020893.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.888

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.888 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC180	NM_020893.6	c.4959A>G	p.Gln1653=	synonymous_variant	37/37	ENST00000529487.3
SUGT1P4-STRA6LP-CCDC180	NR_036528.1	n.6514A>G		non_coding_transcript_exon_variant	51/51
SUGT1P4-STRA6LP-CCDC180	NR_036527.1	n.5932A>G		non_coding_transcript_exon_variant	49/49
SUGT1P4-STRA6LP-CCDC180	NR_036529.1	n.5381A>G		non_coding_transcript_exon_variant	45/45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC180	ENST00000529487.3	c.4959A>G	p.Gln1653=	synonymous_variant	37/37	1	NM_020893.6	P1
CCDC180	ENST00000487976.2	n.3030A>G		non_coding_transcript_exon_variant	3/3	1
CCDC180	ENST00000526038.1	n.6239A>G		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49631 AN: 151896 Hom.: 9971 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.284

GnomAD3 exomes AF: 0.305 AC: 76474 AN: 250414 Hom.: 14971 AF XY: 0.288 AC XY: 39038 AN XY: 135382

Gnomad AFR exome AF: 0.543

Gnomad AMR exome AF: 0.537

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.544

Gnomad SAS exome AF: 0.296

Gnomad FIN exome AF: 0.215

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.231 AC: 336788 AN: 1458372 Hom.: 46778 Cov.: 33 AF XY: 0.230 AC XY: 167056 AN XY: 725616

Gnomad4 AFR exome AF: 0.542

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.566

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.327 AC: 49701 AN: 152014 Hom.: 9989 Cov.: 32 AF XY: 0.329 AC XY: 24455 AN XY: 74310

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.283

Alfa AF: 0.211 Hom.: 8858

Bravo AF: 0.352

Asia WGS AF: 0.390 AC: 1354 AN: 3478

EpiCase AF: 0.190

EpiControl AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	1.5
Dann	Benign	0.60

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: rs11581; hg19: chr9-100139161; COSMIC: COSV63828077; COSMIC: COSV63828077;