rs2227010

Variant names:

• chr3-46370051-G-A
• rs2227010
• ENST00000451485.3:n.572+1193C>T

Variant summary

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

The ENST00000451485.3(CCR5AS):​n.572+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 ENST00000451485.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 21 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000451485.3. 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+1193C>T		intron	N/A
	CCR5AS	NR_185891.1		n.344+1193C>T		intron	N/A
	CCR5	NM_000579.4		c.-448G>A		upstream_gene	N/A	NP_000570.1	Q38L21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5AS	ENST00000451485.3	TSL:3 MANE Select	n.572+1193C>T		intron	N/A
	CCR5AS	ENST00000701879.2		n.462+1193C>T		intron	N/A
	CCR5AS	ENST00000717843.1		n.324+1193C>T		intron	N/A

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

African (AFR) AF: 0.781 AC: 32385 AN: 41446

American (AMR) AF: 0.639 AC: 9757 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1954 AN: 3466

East Asian (EAS) AF: 0.805 AC: 4168 AN: 5176

South Asian (SAS) AF: 0.733 AC: 3518 AN: 4798

European-Finnish (FIN) AF: 0.526 AC: 5552 AN: 10548

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36131 AN: 67910

Other (OTH) AF: 0.632 AC: 1331 AN: 2106

Alfa AF: 0.574 Hom.: 33299

Bravo AF: 0.643

Asia WGS AF: 0.720 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.70
PhyloP100		1.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2227010;

hg19: chr3-46411542;