rs4743077

Positions:

• chr9-97329203-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020893.6(CCDC180):​c.1789-951A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,156 control chromosomes in the GnomAD database, including 24,170 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 (24170 hom., cov: 33)
• Consequence: CCDC180 NM_020893.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC180	NM_020893.6	c.1789-951A>G		intron_variant		ENST00000529487.3	NP_065944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC180	ENST00000529487.3	c.1789-951A>G		intron_variant		1	NM_020893.6	ENSP00000434727.2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83158 AN: 152038 Hom.: 24108 Cov.: 33

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.547 AC: 83278 AN: 152156 Hom.: 24170 Cov.: 33 AF XY: 0.542 AC XY: 40338 AN XY: 74396

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.523

Alfa AF: 0.528 Hom.: 3768

Bravo AF: 0.573

Asia WGS AF: 0.543 AC: 1887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.40

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: rs4743077; hg19: chr9-100091485; COSMIC: COSV63828370; COSMIC: COSV63828370;