ENST00000357422.2:c.-68+13981A>T

Variant names:

• chr3-46224888-A-T
• rs2373156
• ENST00000357422.2:c.-68+13981A>T

Variant summary

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

The ENST00000357422.2(CCR3):​c.-68+13981A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,118 control chromosomes in the GnomAD database, including 3,018 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 0.16 (3018 hom., cov: 32)
• Consequence: CCR3 ENST00000357422.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 6 publications found

Genes affected

CCR3 (HGNC:1604): (C-C motif chemokine receptor 3) The protein encoded by this gene is a receptor for C-C type chemokines. It belongs to family 1 of the G protein-coupled receptors. This receptor binds and responds to a variety of chemokines, including eotaxin (CCL11), eotaxin-3 (CCL26), MCP-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5). It is highly expressed in eosinophils and basophils, and is also detected in TH1 and TH2 cells, as well as in airway epithelial cells. This receptor may contribute to the accumulation and activation of eosinophils and other inflammatory cells in the allergic airway. It is also known to be an entry co-receptor for HIV-1. This gene and seven other chemokine receptor genes form a chemokine receptor gene cluster on the chromosomal region 3p21. Alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR3	XM_006712960.4	c.-68+13981A>T		intron_variant	Intron 1 of 2		XP_006713023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR3	ENST00000357422.2	c.-68+13981A>T		intron_variant	Intron 2 of 3	2		ENSP00000350003.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24439 AN: 152002 Hom.: 3003 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.0774

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.161 AC: 24478 AN: 152118 Hom.: 3018 Cov.: 32 AF XY: 0.162 AC XY: 12060 AN XY: 74380

African (AFR) AF: 0.340 AC: 14093 AN: 41440

American (AMR) AF: 0.102 AC: 1559 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3468

East Asian (EAS) AF: 0.0391 AC: 203 AN: 5190

South Asian (SAS) AF: 0.253 AC: 1221 AN: 4820

European-Finnish (FIN) AF: 0.117 AC: 1234 AN: 10590

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.0773 AC: 5260 AN: 68012

Other (OTH) AF: 0.147 AC: 310 AN: 2110

Alfa AF: 0.123 Hom.: 258

Bravo AF: 0.167

Asia WGS AF: 0.144 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.58
DANN	Benign	0.13
PhyloP100		-1.8
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: rs2373156; hg19: chr3-46266379; COSMIC: COSV107424729;