rs2240478

Positions:

• chr7-75772100-G-A

Variant summary

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

The NM_001371938.1(CCL26):​c.73+4C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,586,878 control chromosomes in the GnomAD database, including 33,940 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 0.21 (3664 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30276 hom.)
• Consequence: CCL26 NM_001371938.1 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0007954
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912

Genes affected

CCL26 (HGNC:10625): (C-C motif chemokine ligand 26) This gene is one of two Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 7. 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 normal peripheral blood eosinophils and basophils. This protein also has antimicrobial activity, displaying an antibacterial effect on S. pneumoniae, S. aureus, Non-typeable H. influenzae, and P. aeruginosa. The product of this gene is one of three related chemokines that specifically activate chemokine receptor CCR3. This chemokine may contribute to the eosinophil accumulation in atopic diseases. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL26	NM_001371938.1	c.73+4C>T		splice_donor_region_variant, intron_variant		ENST00000005180.9
CCL26	NM_001371936.1	c.73+4C>T		splice_donor_region_variant, intron_variant
CCL26	NM_006072.4	c.73+4C>T		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL26	ENST00000005180.9	c.73+4C>T		splice_donor_region_variant, intron_variant		1	NM_001371938.1	P1
CCL26	ENST00000394905.2	c.73+4C>T		splice_donor_region_variant, intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31757 AN: 152010 Hom.: 3651 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.219

GnomAD3 exomes AF: 0.234 AC: 48317 AN: 206616 Hom.: 6736 AF XY: 0.225 AC XY: 24978 AN XY: 111068

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.286

Gnomad SAS exome AF: 0.188

Gnomad FIN exome AF: 0.176

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.197 AC: 283362 AN: 1434750 Hom.: 30276 Cov.: 31 AF XY: 0.196 AC XY: 139735 AN XY: 711840

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.454

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.198

GnomAD4 genome AF: 0.209 AC: 31787 AN: 152128 Hom.: 3664 Cov.: 32 AF XY: 0.212 AC XY: 15793 AN XY: 74366

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.218

Alfa AF: 0.191 Hom.: 4866

Bravo AF: 0.230

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.034
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00080
dbscSNV1_RF	Benign	0.0080
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: rs2240478; hg19: chr7-75401418; COSMIC: COSV50013602;