rs2287936

Positions:

• chr19-8062447-G-A
• chr19-8062447-G-T

Variant summary

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

The NM_005624.4(CCL25):​c.*222G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 567,768 control chromosomes in the GnomAD database, including 2,697 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 0.081 (692 hom., cov: 32)
  • Exomes 𝑓: 0.092 (2005 hom.)
• Consequence: CCL25 NM_005624.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518

Genes affected

CCL25 (HGNC:10624): (C-C motif chemokine ligand 25) This antimicrobial gene belongs to the subfamily of small cytokine CC genes. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity for dendritic cells, thymocytes, and activated macrophages but is inactive on peripheral blood lymphocytes and neutrophils. The product of this gene binds to chemokine receptor CCR9. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL25	NM_005624.4	c.*222G>A		3_prime_UTR_variant	6/6	ENST00000315626.6	NP_005615.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL25	ENST00000315626.6	c.*222G>A		3_prime_UTR_variant	6/6	2	NM_005624.4	ENSP00000324756	A1

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12361 AN: 152018 Hom.: 685 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.0872

Gnomad OTH AF: 0.0834

GnomAD4 exome AF: 0.0915 AC: 38032 AN: 415632 Hom.: 2005 Cov.: 3 AF XY: 0.0916 AC XY: 19991 AN XY: 218340

Gnomad4 AFR exome AF: 0.0259

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.0644

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.0945

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.0841

Gnomad4 OTH exome AF: 0.0853

GnomAD4 genome AF: 0.0814 AC: 12381 AN: 152136 Hom.: 692 Cov.: 32 AF XY: 0.0847 AC XY: 6301 AN XY: 74376

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.0823

Gnomad4 SAS AF: 0.0889

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.0872

Gnomad4 OTH AF: 0.0825

Alfa AF: 0.0821 Hom.: 808

Bravo AF: 0.0814

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.57

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: rs2287936; hg19: chr19-8127331;