3-46203876-G-A

Position:

• chr3-46203876-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001295.3(CCR1):​c.438C>T​(p.Thr146=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000959 in 1,614,170 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (5 hom.)
• Consequence: CCR1 NM_001295.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.23

Genes affected

CCR1 (HGNC:1602): (C-C motif chemokine receptor 1) This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. The ligands of this receptor include macrophage inflammatory protein 1 alpha (MIP-1 alpha), regulated on activation normal T expressed and secreted protein (RANTES), monocyte chemoattractant protein 3 (MCP-3), and myeloid progenitor inhibitory factor-1 (MPIF-1). Chemokines and their receptors mediated signal transduction are critical for the recruitment of effector immune cells to the site of inflammation. Knockout studies of the mouse homolog suggested the roles of this gene in host protection from inflammatory response, and susceptibility to virus and parasite. This gene and other chemokine receptor genes, including CCR2, CCRL2, CCR3, CCR5 and CCXCR1, are found to form a gene cluster on chromosome 3p. [provided by RefSeq, Jul 2008]

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-46203876-G-A is Benign according to our data. Variant chr3-46203876-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 719418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.23 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR1	NM_001295.3	c.438C>T	p.Thr146=	synonymous_variant	2/2	ENST00000296140.4	NP_001286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR1	ENST00000296140.4	c.438C>T	p.Thr146=	synonymous_variant	2/2	1	NM_001295.3	ENSP00000296140	P1
CCR3	ENST00000357422.2	c.-284-6815G>A		intron_variant		2		ENSP00000350003	P1

Frequencies

GnomAD3 genomes AF: 0.000637 AC: 97 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000526 AC: 132 AN: 251098 Hom.: 0 AF XY: 0.000582 AC XY: 79 AN XY: 135686

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.000855

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000993 AC: 1451 AN: 1461888 Hom.: 5 Cov.: 33 AF XY: 0.000946 AC XY: 688 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.000262

Gnomad4 NFE exome AF: 0.00117

Gnomad4 OTH exome AF: 0.00126

GnomAD4 genome AF: 0.000637 AC: 97 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.000645 AC XY: 48 AN XY: 74452

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00113

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000869 Hom.: 0

Bravo AF: 0.000567

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.076
DANN	Benign	0.87

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: rs146268408; hg19: chr3-46245367; COSMIC: COSV56122051;