9-97376879-A-G

Variant names:

• chr9-97376879-A-G
• rs11581
• NM_020893.6:c.4959A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020893.6(CCDC180):​c.4959A>G​(p.Gln1653Gln) 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
• Publications: 15 publications found

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:53835): (SUGT1P4-STRA6LP-CCDC180 readthrough) This locus represents a set of read-through transcripts spanning an upstream pseudogene (GeneID:100499484) extending into a downstream protein-coding locus (GeneID:100499483). All of the read-through transcripts are candidates for nonsense-mediated decay (NMD), so they are not thought to express a protein. [provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCDC180	NM_020893.6	c.4959A>G	p.Gln1653Gln	synonymous_variant	Exon 37 of 37	ENST00000529487.3	NP_065944.3
SUGT1P4-STRA6LP-CCDC180	NR_036527.1	n.5932A>G		non_coding_transcript_exon_variant	Exon 49 of 49
SUGT1P4-STRA6LP-CCDC180	NR_036528.1	n.6514A>G		non_coding_transcript_exon_variant	Exon 51 of 51
SUGT1P4-STRA6LP-CCDC180	NR_036529.1	n.5381A>G		non_coding_transcript_exon_variant	Exon 45 of 45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC180	ENST00000529487.3	c.4959A>G	p.Gln1653Gln	synonymous_variant	Exon 37 of 37	1	NM_020893.6	ENSP00000434727.2

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

GnomAD2 exomes AF: 0.305 AC: 76474 AN: 250414 AF XY: 0.288

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 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

African (AFR) AF: 0.542 AC: 18095 AN: 33394

American (AMR) AF: 0.520 AC: 23225 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3723 AN: 26096

East Asian (EAS) AF: 0.566 AC: 22422 AN: 39646

South Asian (SAS) AF: 0.297 AC: 25576 AN: 86118

European-Finnish (FIN) AF: 0.216 AC: 11464 AN: 52968

Middle Eastern (MID) AF: 0.161 AC: 754 AN: 4686

European-Non Finnish (NFE) AF: 0.195 AC: 216814 AN: 1110604

Other (OTH) AF: 0.244 AC: 14715 AN: 60200

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

African (AFR) AF: 0.537 AC: 22256 AN: 41434

American (AMR) AF: 0.401 AC: 6127 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3462

East Asian (EAS) AF: 0.530 AC: 2731 AN: 5150

South Asian (SAS) AF: 0.293 AC: 1410 AN: 4818

European-Finnish (FIN) AF: 0.222 AC: 2347 AN: 10584

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13613 AN: 67966

Other (OTH) AF: 0.283 AC: 599 AN: 2116

Alfa AF: 0.225 Hom.: 13090

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
PhyloP100		0.89
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: rs11581; hg19: chr9-100139161; COSMIC: COSV63828077; COSMIC: COSV63828077;