rs3054375

Positions:

• chr3-46371771-CAG-C
• chr3-46371771-CAG-CAGAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001394783.1(CCR5):​c.-12+785_-12+786delGA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7754 hom., cov: 0)
• Consequence: CCR5 NM_001394783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.790

Genes affected

CCR5 (HGNC:1606): (C-C motif chemokine receptor 5) 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. This protein is expressed by T cells and macrophages, and is known to be an important co-receptor for macrophage-tropic virus, including HIV, to enter host cells. Defective alleles of this gene have been associated with the HIV infection resistance. The ligands of this receptor include monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein 1 alpha (MIP-1 alpha), macrophage inflammatory protein 1 beta (MIP-1 beta) and regulated on activation normal T expressed and secreted protein (RANTES). Expression of this gene was also detected in a promyeloblastic cell line, suggesting that this protein may play a role in granulocyte lineage proliferation and differentiation. This gene is located at the chemokine receptor gene cluster region. An allelic polymorphism in this gene results in both functional and non-functional alleles; the reference genome represents the functional allele. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2015]

CCR5AS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR5	NM_001394783.1	c.-12+785_-12+786delGA		intron_variant		ENST00000292303.5	NP_001381712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR5	ENST00000292303.5	c.-12+785_-12+786delGA		intron_variant		1	NM_001394783.1	ENSP00000292303.4
CCR5AS	ENST00000451485.2	n.392-356_392-355delCT		intron_variant		3
CCR5AS	ENST00000701879.1	n.174-356_174-355delCT		intron_variant

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45576 AN: 151858 Hom.: 7753 Cov.: 0

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.300 AC: 45583 AN: 151976 Hom.: 7754 Cov.: 0 AF XY: 0.304 AC XY: 22577 AN XY: 74288

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.346

Alfa AF: 0.301 Hom.: 910

Bravo AF: 0.297

Asia WGS AF: 0.413 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3054375; hg19: chr3-46413262;