rs9797

Positions:

• chr8-27734332-G-A

Variant summary

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

The NM_018246.3(CCDC25):​c.*1884C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,036 control chromosomes in the GnomAD database, including 14,324 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 0.42 (14321 hom., cov: 32)
  • Exomes 𝑓: 0.50 (3 hom.)
• Consequence: CCDC25 NM_018246.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC25	NM_018246.3	c.*1884C>T		3_prime_UTR_variant	9/9	ENST00000356537.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC25	ENST00000356537.9	c.*1884C>T		3_prime_UTR_variant	9/9	1	NM_018246.3	P1
CCDC25	ENST00000520486.5	c.*2330C>T		3_prime_UTR_variant, NMD_transcript_variant	8/8	1
	ENST00000521510.2	n.647+771G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64451 AN: 151898 Hom.: 14325 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.500 AC: 9 AN: 18 Hom.: 3 Cov.: 0 AF XY: 0.500 AC XY: 6 AN XY: 12

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.424 AC: 64471 AN: 152018 Hom.: 14321 Cov.: 32 AF XY: 0.426 AC XY: 31678 AN XY: 74322

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.429

Alfa AF: 0.471 Hom.: 29358

Bravo AF: 0.407

Asia WGS AF: 0.258 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.5
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9797; hg19: chr8-27591849;