rs2240478

Variant names:

• chr7-75772100-G-A
• rs2240478
• NM_001371938.1:c.73+4C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-75772100-G-A
• chr7-75772100-G-C
• chr7-75772100-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371938.1(CCL26):​c.73+4C>T variant causes a splice 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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_region, intron
• Scores: Splicing: ADA: 0.0007954
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912
• Publications: 17 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371938.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL26	NM_001371938.1	MANE Select	c.73+4C>T		splice_region intron	N/A	NP_001358867.1
	CCL26	NM_001371936.1		c.73+4C>T		splice_region intron	N/A	NP_001358865.1
	CCL26	NM_006072.4		c.73+4C>T		splice_region intron	N/A	NP_006063.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL26	ENST00000005180.9	TSL:1 MANE Select	c.73+4C>T		splice_region intron	N/A	ENSP00000005180.4
	CCL26	ENST00000394905.2	TSL:1	c.73+4C>T		splice_region intron	N/A	ENSP00000378365.2

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

GnomAD2 exomes AF: 0.234 AC: 48317 AN: 206616 AF XY: 0.225

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 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

African (AFR) AF: 0.202 AC: 6626 AN: 32740

American (AMR) AF: 0.454 AC: 17918 AN: 39474

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3300 AN: 25644

East Asian (EAS) AF: 0.309 AC: 11781 AN: 38084

South Asian (SAS) AF: 0.189 AC: 15788 AN: 83572

European-Finnish (FIN) AF: 0.173 AC: 8981 AN: 52024

Middle Eastern (MID) AF: 0.200 AC: 1135 AN: 5686

European-Non Finnish (NFE) AF: 0.188 AC: 206043 AN: 1098108

Other (OTH) AF: 0.198 AC: 11790 AN: 59418

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

African (AFR) AF: 0.202 AC: 8392 AN: 41502

American (AMR) AF: 0.350 AC: 5346 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3470

East Asian (EAS) AF: 0.293 AC: 1510 AN: 5162

South Asian (SAS) AF: 0.201 AC: 968 AN: 4816

European-Finnish (FIN) AF: 0.187 AC: 1982 AN: 10598

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12357 AN: 68000

Other (OTH) AF: 0.218 AC: 459 AN: 2106

Alfa AF: 0.195 Hom.: 12617

Bravo AF: 0.230

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.034
DANN	Benign	0.79
PhyloP100		-0.91
PromoterAI		-0.062	Neutral
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240478; hg19: chr7-75401418; COSMIC: COSV50013602;