rs2227010

Variant names:

• chr3-46370051-G-A
• rs2227010
• ENST00000451485.2:n.565+1193C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000451485.2(CCR5AS):​n.565+1193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,920 control chromosomes in the GnomAD database, including 31,104 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 0.63 (31104 hom., cov: 31)
• Consequence: CCR5AS ENST00000451485.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR5AS	NR_125406.2	n.572+1193C>T		intron_variant	Intron 3 of 3
CCR5AS	NR_185891.1	n.344+1193C>T		intron_variant	Intron 2 of 2
CCR5	NM_000579.4	c.-448G>A		upstream_gene_variant			NP_000570.1
CCR5	NM_001100168.2	c.-213G>A		upstream_gene_variant			NP_001093638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR5AS	ENST00000451485.2	n.565+1193C>T		intron_variant	Intron 3 of 3	3
CCR5AS	ENST00000701879.1	n.347+1193C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95473 AN: 151804 Hom.: 31059 Cov.: 31

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.629 AC: 95560 AN: 151920 Hom.: 31104 Cov.: 31 AF XY: 0.634 AC XY: 47103 AN XY: 74238

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.632

Alfa AF: 0.579 Hom.: 3389

Bravo AF: 0.643

Asia WGS AF: 0.720 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2227010; hg19: chr3-46411542;