rs2856758

Variant names:

• chr3-46370170-A-G
• rs2856758
• ENST00000451485.3:n.572+1074T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000579.4(CCR5):​c.-329A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,206 control chromosomes in the GnomAD database, including 1,099 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1099 hom., cov: 31)
• Consequence: CCR5 NM_000579.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• Publications: 37 publications found

Genes affected

CCR5AS (HGNC:54398): (CCR5 antisense RNA)

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000579.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5AS	NR_125406.2	MANE Select	n.572+1074T>C		intron	N/A
	CCR5	NM_000579.4		c.-329A>G		5_prime_UTR	Exon 1 of 3	NP_000570.1	Q38L21
	CCR5	NM_001100168.2		c.-94A>G		5_prime_UTR	Exon 1 of 3	NP_001093638.1	Q38L21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5AS	ENST00000451485.3	TSL:3 MANE Select	n.572+1074T>C		intron	N/A
	CCR5AS	ENST00000701879.2		n.462+1074T>C		intron	N/A
	CCR5AS	ENST00000717843.1		n.324+1074T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16542 AN: 152088 Hom.: 1099 Cov.: 31

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.0824

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.109 AC: 16550 AN: 152206 Hom.: 1099 Cov.: 31 AF XY: 0.106 AC XY: 7864 AN XY: 74412

African (AFR) AF: 0.0615 AC: 2552 AN: 41526

American (AMR) AF: 0.0825 AC: 1262 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0236 AC: 114 AN: 4824

European-Finnish (FIN) AF: 0.152 AC: 1611 AN: 10594

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10016 AN: 67994

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.130 Hom.: 518

Bravo AF: 0.102

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.56
PhyloP100		-0.55
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2856758; hg19: chr3-46411661;