3-46203247-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001295.3(CCR1):c.1067G>A(p.Ter356=) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,610,120 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0097 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (28 hom.)
• Consequence: CCR1 NM_001295.3 stop_retained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.836

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 3-46203247-C-T is Benign according to our data. Variant chr3-46203247-C-T is described in ClinVar as [Benign]. Clinvar id is 775865.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.836 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00973 (1481/152242) while in subpopulation AFR AF= 0.0338 (1403/41534). AF 95% confidence interval is 0.0323. There are 27 homozygotes in gnomad4. There are 710 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR1	NM_001295.3	c.1067G>A	p.Ter356=	stop_retained_variant	2/2	ENST00000296140.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR1	ENST00000296140.4	c.1067G>A	p.Ter356=	stop_retained_variant	2/2	1	NM_001295.3	P1
CCR3	ENST00000357422.2	c.-284-7444C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.00970 AC: 1476 AN: 152124 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00246 AC: 612 AN: 248296 Hom.: 9 AF XY: 0.00192 AC XY: 257 AN XY: 134180

Gnomad AFR exome AF: 0.0322

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000197

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00111 AC: 1623 AN: 1457878 Hom.: 28 Cov.: 31 AF XY: 0.00102 AC XY: 738 AN XY: 724848

Gnomad4 AFR exome AF: 0.0353

Gnomad4 AMR exome AF: 0.00166

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000932

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000161

Gnomad4 OTH exome AF: 0.00284

GnomAD4 genome AF: 0.00973 AC: 1481 AN: 152242 Hom.: 27 Cov.: 32 AF XY: 0.00954 AC XY: 710 AN XY: 74442

Gnomad4 AFR AF: 0.0338

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00463 Hom.: 9

Bravo AF: 0.0108

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000475

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

Jul 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	13
Dann	Benign	0.66

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: rs41413045; hg19: chr3-46244738;