3-112637923-T-C

Position:

• chr3-112637923-T-C

Variant summary

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

The NM_199511.3(CCDC80):​c.1878+105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 1,502,414 control chromosomes in the GnomAD database, including 368,975 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 0.68 (35893 hom., cov: 32)
  • Exomes 𝑓: 0.70 (333082 hom.)
• Consequence: CCDC80 NM_199511.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

Genes affected

CCDC80 (HGNC:30649): (coiled-coil domain containing 80) Predicted to enable glycosaminoglycan binding activity. Predicted to act upstream of or within extracellular matrix organization; positive regulation of cell-substrate adhesion; and response to bacterium. Predicted to be located in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC80	NM_199511.3	c.1878+105A>G		intron_variant		ENST00000206423.8
CCDC80	NM_199512.3	c.1878+105A>G		intron_variant
CCDC80	XM_047447495.1	c.1911+105A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC80	ENST00000206423.8	c.1878+105A>G		intron_variant		1	NM_199511.3	P1
CCDC80	ENST00000439685.6	c.1878+105A>G		intron_variant		1		P1
CCDC80	ENST00000461431.1	c.70+105A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103996 AN: 151930 Hom.: 35865 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.701 AC: 946581 AN: 1350364 Hom.: 333082 AF XY: 0.703 AC XY: 466293 AN XY: 663516

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.699

Gnomad4 EAS exome AF: 0.869

Gnomad4 SAS exome AF: 0.779

Gnomad4 FIN exome AF: 0.747

Gnomad4 NFE exome AF: 0.690

Gnomad4 OTH exome AF: 0.701

GnomAD4 genome AF: 0.684 AC: 104077 AN: 152050 Hom.: 35893 Cov.: 32 AF XY: 0.689 AC XY: 51230 AN XY: 74326

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.629

Alfa AF: 0.697 Hom.: 23369

Bravo AF: 0.674

Asia WGS AF: 0.790 AC: 2747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.9
DANN	Benign	0.85

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: rs2279531; hg19: chr3-112356770;