7-75770600-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL26	NM_001371938.1	c.189-811G>A		intron_variant	Intron 2 of 2	ENST00000005180.9	NP_001358867.1
CCL26	NM_001371936.1	c.189-811G>A		intron_variant	Intron 3 of 3		NP_001358865.1
CCL26	NM_006072.4	c.189-811G>A		intron_variant	Intron 3 of 3		NP_006063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL26	ENST00000005180.9	c.189-811G>A		intron_variant	Intron 2 of 2	1	NM_001371938.1	ENSP00000005180.4
CCL26	ENST00000394905.2	c.189-811G>A		intron_variant	Intron 3 of 3	1		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

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.279

Alfa AF: 0.296 Hom.: 905

Bravo AF: 0.300

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.86

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: rs6965556; hg19: chr7-75399918;