7-75770600-C-T

Variant names:

• chr7-75770600-C-T
• rs6965556
• NM_001371938.1:c.189-811G>A

Variant summary

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

The NM_001371938.1(CCL26):​c.189-811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,734 control chromosomes in the GnomAD database, including 7,499 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 0.30 (7499 hom., cov: 31)
• Consequence: CCL26 NM_001371938.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 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.189-811G>A		intron	N/A	NP_001358867.1
	CCL26	NM_001371936.1		c.189-811G>A		intron	N/A	NP_001358865.1
	CCL26	NM_006072.4		c.189-811G>A		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.189-811G>A		intron	N/A	ENSP00000005180.4
	CCL26	ENST00000394905.2	TSL:1	c.189-811G>A		intron	N/A	ENSP00000378365.2

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45276 AN: 151616 Hom.: 7480 Cov.: 31

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.299 AC: 45340 AN: 151734 Hom.: 7499 Cov.: 31 AF XY: 0.295 AC XY: 21897 AN XY: 74112

African (AFR) AF: 0.441 AC: 18240 AN: 41338

American (AMR) AF: 0.240 AC: 3658 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 855 AN: 3468

East Asian (EAS) AF: 0.116 AC: 599 AN: 5150

South Asian (SAS) AF: 0.212 AC: 1019 AN: 4814

European-Finnish (FIN) AF: 0.284 AC: 2976 AN: 10492

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.252 AC: 17107 AN: 67950

Other (OTH) AF: 0.279 AC: 586 AN: 2104

Alfa AF: 0.301 Hom.: 974

Bravo AF: 0.300

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.86
PhyloP100		-0.61
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: rs6965556; hg19: chr7-75399918;