19-8062447-G-T

Variant names:

• chr19-8062447-G-T
• rs2287936
• NM_005624.4:c.*222G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005624.4(CCL25):​c.*222G>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 0.0000144 in 415,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: CCL25 NM_005624.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 9 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005624.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL25	NM_005624.4	MANE Select	c.*222G>T		3_prime_UTR	Exon 6 of 6	NP_005615.2
	CCL25	NM_001394634.1		c.*222G>T		3_prime_UTR	Exon 7 of 7	NP_001381563.1	O15444-1
	CCL25	NM_001394635.1		c.*222G>T		3_prime_UTR	Exon 7 of 7	NP_001381564.1	O15444-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL25	ENST00000315626.6	TSL:2 MANE Select	c.*222G>T		3_prime_UTR	Exon 6 of 6	ENSP00000324756.6	O15444-1
	CCL25	ENST00000390669.7	TSL:1	c.*222G>T		3_prime_UTR	Exon 5 of 5	ENSP00000375086.3	O15444-1
	CCL25	ENST00000680506.1		c.*222G>T		3_prime_UTR	Exon 7 of 7	ENSP00000505422.1	O15444-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000144 AC: 6 AN: 415980 Hom.: 0 Cov.: 3 AF XY: 0.00000915 AC XY: 2 AN XY: 218536

African (AFR) AF: 0.00 AC: 0 AN: 11754

American (AMR) AF: 0.00 AC: 0 AN: 17772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12850

East Asian (EAS) AF: 0.00 AC: 0 AN: 29266

South Asian (SAS) AF: 0.00 AC: 0 AN: 42564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1822

European-Non Finnish (NFE) AF: 0.0000241 AC: 6 AN: 248846

Other (OTH) AF: 0.00 AC: 0 AN: 24092

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1053

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		-0.52

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2287936;

hg19: chr19-8127331;