rs11951515

Positions:

• chr5-43382756-T-C

Variant summary

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

The NM_148672.3(CCL28):​c.192-704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,072 control chromosomes in the GnomAD database, including 22,054 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 0.53 (22054 hom., cov: 32)
• Consequence: CCL28 NM_148672.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

Genes affected

CCL28 (HGNC:17700): (C-C motif chemokine ligand 28) 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 resting CD4 or CD8 T cells and eosinophils. The product of this gene binds to chemokine receptors CCR3 and CCR10. This chemokine may play a role in the physiology of extracutaneous epithelial tissues, including diverse mucosal organs. Multiple transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL28	NM_148672.3	c.192-704A>G		intron_variant		ENST00000361115.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL28	ENST00000361115.4	c.192-704A>G		intron_variant		1	NM_148672.3	P1
CCL28	ENST00000513525.1	c.51-704A>G		intron_variant		1
CCL28	ENST00000489442.5	c.192-704A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80441 AN: 151954 Hom.: 22060 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.529 AC: 80449 AN: 152072 Hom.: 22054 Cov.: 32 AF XY: 0.525 AC XY: 39019 AN XY: 74364

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.555

Alfa AF: 0.553 Hom.: 9261

Bravo AF: 0.516

Asia WGS AF: 0.277 AC: 967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.0
DANN	Benign	0.88

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: rs11951515; hg19: chr5-43382858;