rs9797

Variant names:

• chr8-27734332-G-A
• rs9797
• NM_018246.3:c.*1884C>T

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]

ENSG00000253875 (HGNC:):

SCARA3 (HGNC:19000): (scavenger receptor class A member 3) This gene encodes a macrophage scavenger receptor-like protein. This protein has been shown to deplete reactive oxygen species, and thus play an important role in protecting cells from oxidative stress. The expression of this gene is induced by oxidative stress. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
CCDC25	NM_018246.3	c.*1884C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000356537.9	NP_060716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC25	ENST00000356537	c.*1884C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_018246.3	ENSP00000348933.4
CCDC25	ENST00000520486.5	n.*2330C>T		non_coding_transcript_exon_variant	Exon 8 of 8	1		ENSP00000427714.1
CCDC25	ENST00000520486.5	n.*2330C>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000427714.1
ENSG00000253875	ENST00000521510.2	n.647+771G>A		intron_variant	Intron 1 of 3	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;