rs11671930

Positions:

• chr19-8052424-T-C

Variant summary

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

The NM_001394635.1(CCL25):​c.-131T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 151,702 control chromosomes in the GnomAD database, including 1,424 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 0.12 (1424 hom., cov: 29)
• Consequence: CCL25 NM_001394635.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL25	NM_001394635.1	c.-131T>C		5_prime_UTR_variant	1/7		NP_001381564.1
CCL25	NM_001394636.1	c.-196T>C		5_prime_UTR_variant	1/7		NP_001381565.1
CCL25	NM_001394637.1	c.-206T>C		5_prime_UTR_variant	1/7		NP_001381566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL25	ENST00000680506	c.-196T>C		5_prime_UTR_variant	1/7			ENSP00000505422.1
CCL25	ENST00000680450	c.-206T>C		5_prime_UTR_variant	1/7			ENSP00000506202.1
CCL25	ENST00000681526	c.-131T>C		5_prime_UTR_variant	1/7			ENSP00000505387.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18479 AN: 151584 Hom.: 1427 Cov.: 29

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.161

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.122 AC: 18466 AN: 151702 Hom.: 1424 Cov.: 29 AF XY: 0.118 AC XY: 8758 AN XY: 74100

Gnomad4 AFR AF: 0.0372

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0612

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.160

Alfa AF: 0.167 Hom.: 2998

Bravo AF: 0.117

Asia WGS AF: 0.0390 AC: 136 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	6.0
DANN	Benign	0.48

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: rs11671930; hg19: chr19-8117308;