9-97325063-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.1416A>G(p.Ser472=) 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

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=-0.92).
• 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/exons	MANE	UniProt
CCDC180	NM_020893.6	c.1416A>G	p.Ser472=	synonymous_variant	14/37	ENST00000529487.3
SUGT1P4-STRA6LP-CCDC180	NR_036528.1	n.2971A>G		non_coding_transcript_exon_variant	28/51

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC180	ENST00000529487.3	c.1416A>G	p.Ser472=	synonymous_variant	14/37	1	NM_020893.6	P1
CCDC180	ENST00000494917.6	n.1619A>G		non_coding_transcript_exon_variant	15/20	1
CCDC180	ENST00000460482.6	n.1750A>G		non_coding_transcript_exon_variant	15/21	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

GnomAD3 exomes AF: 0.531 AC: 132809 AN: 250266 Hom.: 37313 AF XY: 0.520 AC XY: 70331 AN XY: 135246

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 SAS exome AF: 0.567

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

Gnomad4 AFR exome AF: 0.742

Gnomad4 AMR exome AF: 0.717

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.592

Gnomad4 SAS exome AF: 0.567

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.526

Alfa AF: 0.462 Hom.: 6689

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

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: rs3747496; hg19: chr9-100087345; COSMIC: COSV63827054;