9-97325063-A-G

Variant names:

• chr9-97325063-A-G
• rs3747496
• NM_020893.6:c.1416A>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.1416A>G​(p.Ser472Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,613,192 control chromosomes in the GnomAD database, including 197,954 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 0.55 (24421 hom., cov: 32)
  • Exomes 𝑓: 0.48 (173533 hom.)
• Consequence: CCDC180 NM_020893.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 22 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 (REVEL=0.012).
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC180	NM_020893.6	c.1416A>G	p.Ser472Ser	synonymous_variant	Exon 14 of 37	ENST00000529487.3	NP_065944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC180	ENST00000529487.3	c.1416A>G	p.Ser472Ser	synonymous_variant	Exon 14 of 37	1	NM_020893.6	ENSP00000434727.2

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83486 AN: 151912 Hom.: 24359 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.529

GnomAD2 exomes AF: 0.531 AC: 132809 AN: 250266 AF XY: 0.520

Gnomad AFR exome AF: 0.740

Gnomad AMR exome AF: 0.729

Gnomad ASJ exome AF: 0.455

Gnomad EAS exome AF: 0.582

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.463

Gnomad OTH exome AF: 0.495

GnomAD4 exome AF: 0.481 AC: 702780 AN: 1461162 Hom.: 173533 Cov.: 40 AF XY: 0.482 AC XY: 350305 AN XY: 726850

African (AFR) AF: 0.742 AC: 24824 AN: 33476

American (AMR) AF: 0.717 AC: 32051 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 11756 AN: 26116

East Asian (EAS) AF: 0.592 AC: 23491 AN: 39672

South Asian (SAS) AF: 0.567 AC: 48856 AN: 86190

European-Finnish (FIN) AF: 0.369 AC: 19693 AN: 53344

Middle Eastern (MID) AF: 0.501 AC: 2884 AN: 5756

European-Non Finnish (NFE) AF: 0.458 AC: 509034 AN: 1111558

Other (OTH) AF: 0.500 AC: 30191 AN: 60356

GnomAD4 genome AF: 0.550 AC: 83606 AN: 152030 Hom.: 24421 Cov.: 32 AF XY: 0.545 AC XY: 40466 AN XY: 74314

African (AFR) AF: 0.735 AC: 30491 AN: 41478

American (AMR) AF: 0.616 AC: 9401 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3466

East Asian (EAS) AF: 0.578 AC: 2984 AN: 5164

South Asian (SAS) AF: 0.548 AC: 2633 AN: 4808

European-Finnish (FIN) AF: 0.362 AC: 3826 AN: 10582

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.459 AC: 31179 AN: 67958

Other (OTH) AF: 0.526 AC: 1111 AN: 2114

Alfa AF: 0.458 Hom.: 30098

Bravo AF: 0.576

Asia WGS AF: 0.544 AC: 1890 AN: 3478

EpiCase AF: 0.469

EpiControl AF: 0.459

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.31
PhyloP100		-1.0
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: rs3747496; hg19: chr9-100087345; COSMIC: COSV63827054;