rs2302009

chr7-75769680-A-Cchr7-75769680-A-Gchr7-75769680-A-T

Variant summary

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

The NM_001371938.1(CCL26):c.*13T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,581,242 control chromosomes in the GnomAD database, including 52,309 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 0.29 (6810 hom., cov: 32)
  • Exomes 𝑓: 0.25 (45499 hom.)
• Consequence: CCL26 NM_001371938.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL26	NM_001371938.1	c.*13T>G		3_prime_UTR_variant	3/3	ENST00000005180.9
CCL26	NM_001371936.1	c.*13T>G		3_prime_UTR_variant	4/4
CCL26	NM_006072.4	c.*13T>G		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL26	ENST00000005180.9	c.*13T>G		3_prime_UTR_variant	3/3	1	NM_001371938.1	P1
CCL26	ENST00000394905.2	c.*13T>G		3_prime_UTR_variant	4/4	1		P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43720 AN: 152044 Hom.: 6796 Cov.: 32

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.271

GnomAD3 exomes AF: 0.244 AC: 61138 AN: 250758 Hom.: 7958 AF XY: 0.241 AC XY: 32659 AN XY: 135558

Gnomad AFR exome AF: 0.404

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.126

Gnomad SAS exome AF: 0.219

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.251

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.248 AC: 354880 AN: 1429080 Hom.: 45499 Cov.: 25 AF XY: 0.247 AC XY: 176312 AN XY: 713004

Gnomad4 AFR exome AF: 0.410

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.288 AC: 43772 AN: 152162 Hom.: 6810 Cov.: 32 AF XY: 0.285 AC XY: 21181 AN XY: 74378

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.269

Alfa AF: 0.250 Hom.: 9065

Bravo AF: 0.287

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.9
Dann	Benign	0.70

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: rs2302009; hg19: chr7-75398998; COSMIC: COSV50013605;