rs2280884

Positions:

• chr8-27756621-A-G

Variant summary

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

The NM_018246.3(CCDC25):​c.168+98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 815,666 control chromosomes in the GnomAD database, including 79,847 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 0.44 (14691 hom., cov: 32)
  • Exomes 𝑓: 0.44 (65156 hom.)
• Consequence: CCDC25 NM_018246.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.894

Genes affected

CCDC25 (HGNC:25591): (coiled-coil domain containing 25) Enables DNA binding activity. Involved in positive regulation of cell motility. Located in endomembrane system. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253875 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC25	NM_018246.3	c.168+98T>C		intron_variant		ENST00000356537.9	NP_060716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC25	ENST00000356537.9	c.168+98T>C		intron_variant		1	NM_018246.3	ENSP00000348933.4

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66184 AN: 151900 Hom.: 14661 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.437 AC: 290264 AN: 663646 Hom.: 65156 Cov.: 9 AF XY: 0.433 AC XY: 152557 AN XY: 352038

Gnomad4 AFR exome AF: 0.448

Gnomad4 AMR exome AF: 0.593

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.627

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.383

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.436 AC: 66275 AN: 152020 Hom.: 14691 Cov.: 32 AF XY: 0.435 AC XY: 32314 AN XY: 74312

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.426

Alfa AF: 0.424 Hom.: 22906

Bravo AF: 0.449

Asia WGS AF: 0.554 AC: 1924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	0.23

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: rs2280884; hg19: chr8-27614138;