3-46203933-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001295.3(CCR1):c.381G>A(p.Leu127=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,614,062 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (155 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (138 hom.)
• Consequence: CCR1 NM_001295.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.23

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 3-46203933-C-T is Benign according to our data. Variant chr3-46203933-C-T is described in ClinVar as [Benign]. Clinvar id is 791924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR1	NM_001295.3	c.381G>A	p.Leu127=	synonymous_variant	2/2	ENST00000296140.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR1	ENST00000296140.4	c.381G>A	p.Leu127=	synonymous_variant	2/2	1	NM_001295.3	P1
CCR3	ENST00000357422.2	c.-284-6758C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3717 AN: 152072 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.0264

GnomAD3 exomes AF: 0.00771 AC: 1936 AN: 251018 Hom.: 57 AF XY: 0.00623 AC XY: 845 AN XY: 135636

Gnomad AFR exome AF: 0.0850

Gnomad AMR exome AF: 0.00703

Gnomad ASJ exome AF: 0.00924

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00148

Gnomad OTH exome AF: 0.00702

GnomAD4 exome AF: 0.00390 AC: 5704 AN: 1461874 Hom.: 138 Cov.: 33 AF XY: 0.00356 AC XY: 2590 AN XY: 727232

Gnomad4 AFR exome AF: 0.0851

Gnomad4 AMR exome AF: 0.00838

Gnomad4 ASJ exome AF: 0.00930

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.00137

Gnomad4 OTH exome AF: 0.00974

GnomAD4 genome AF: 0.0245 AC: 3734 AN: 152188 Hom.: 155 Cov.: 32 AF XY: 0.0226 AC XY: 1682 AN XY: 74396

Gnomad4 AFR AF: 0.0796

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00129

Gnomad4 OTH AF: 0.0261

Alfa AF: 0.00867 Hom.: 40

Bravo AF: 0.0288

Asia WGS AF: 0.00982 AC: 34 AN: 3478

EpiCase AF: 0.00218

EpiControl AF: 0.00213

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	-0.45
Cadd	Benign	8.0
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3136664; hg19: chr3-46245424;