3-46203411-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.903C>T(p.Tyr301=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,614,174 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (4 hom.)
• Consequence: CCR1 NM_001295.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0760

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=-0.83).
• BP6: Variant 3-46203411-G-A is Benign according to our data. Variant chr3-46203411-G-A is described in ClinVar as [Benign]. Clinvar id is 771853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.076 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR1	NM_001295.3	c.903C>T	p.Tyr301=	synonymous_variant	2/2	ENST00000296140.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR1	ENST00000296140.4	c.903C>T	p.Tyr301=	synonymous_variant	2/2	1	NM_001295.3	P1
CCR3	ENST00000357422.2	c.-284-7280G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 249 AN: 152176 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.00193 AC: 484 AN: 251146 Hom.: 1 AF XY: 0.00195 AC XY: 264 AN XY: 135718

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00160

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00150 AC: 2191 AN: 1461880 Hom.: 4 Cov.: 33 AF XY: 0.00152 AC XY: 1104 AN XY: 727242

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.00400

Gnomad4 ASJ exome AF: 0.0147

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000441

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.00119

Gnomad4 OTH exome AF: 0.00298

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152294 Hom.: 2 Cov.: 32 AF XY: 0.00153 AC XY: 114 AN XY: 74474

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00346

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00159

Gnomad4 OTH AF: 0.00333

Alfa AF: 0.00218 Hom.: 1

Bravo AF: 0.00219

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00255

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.36
Dann	Benign	0.76

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: rs141128686; hg19: chr3-46244902; COSMIC: COSV99946633;