chr7-75769680-A-C

Variant names:

• chr7-75769680-A-C
• rs2302009
• NM_001371938.1:c.*13T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCL26	NM_001371938.1	c.*13T>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000005180.9	NP_001358867.1
CCL26	NM_001371936.1	c.*13T>G		3_prime_UTR_variant	Exon 4 of 4		NP_001358865.1
CCL26	NM_006072.4	c.*13T>G		3_prime_UTR_variant	Exon 4 of 4		NP_006063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL26	ENST00000005180.9	c.*13T>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_001371938.1	ENSP00000005180.4
CCL26	ENST00000394905.2	c.*13T>G		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000378365.2

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

GnomAD2 exomes AF: 0.244 AC: 61138 AN: 250758 AF XY: 0.241

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 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

African (AFR) AF: 0.410 AC: 13472 AN: 32832

American (AMR) AF: 0.196 AC: 8744 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 6475 AN: 25902

East Asian (EAS) AF: 0.103 AC: 4086 AN: 39512

South Asian (SAS) AF: 0.223 AC: 19125 AN: 85600

European-Finnish (FIN) AF: 0.297 AC: 15852 AN: 53364

Middle Eastern (MID) AF: 0.226 AC: 1289 AN: 5710

European-Non Finnish (NFE) AF: 0.250 AC: 270836 AN: 1082310

Other (OTH) AF: 0.253 AC: 15001 AN: 59200

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

African (AFR) AF: 0.401 AC: 16649 AN: 41508

American (AMR) AF: 0.236 AC: 3604 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3472

East Asian (EAS) AF: 0.115 AC: 598 AN: 5182

South Asian (SAS) AF: 0.210 AC: 1014 AN: 4826

European-Finnish (FIN) AF: 0.290 AC: 3067 AN: 10590

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17115 AN: 67996

Other (OTH) AF: 0.269 AC: 567 AN: 2110

Alfa AF: 0.260 Hom.: 17027

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
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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