rs2734648

Variant names:

• chr3-46370349-G-C
• rs2734648
• ENST00000451485.3:n.572+895C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-46370349-G-C
• chr3-46370349-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000451485.3(CCR5AS):​n.572+895C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
• Consequence: CCR5AS ENST00000451485.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 41 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR5AS	NR_125406.2	n.572+895C>G		intron_variant	Intron 3 of 3	ENST00000451485.3
CCR5	NM_000579.4	c.-301+151G>C		intron_variant	Intron 1 of 2		NP_000570.1
CCR5	NM_001100168.2	c.-66+151G>C		intron_variant	Intron 1 of 2		NP_001093638.1
CCR5AS	NR_185891.1	n.344+895C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR5AS	ENST00000451485.3	n.572+895C>G		intron_variant	Intron 3 of 3	3	NR_125406.2
CCR5AS	ENST00000701879.2	n.462+895C>G		intron_variant	Intron 2 of 2
CCR5AS	ENST00000717843.1	n.324+895C>G		intron_variant	Intron 2 of 3
CCR5AS	ENST00000741276.1	n.335+895C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 29

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

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.46
PhyloP100		-0.042

Splicing

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

Other links and lift over

dbSNP: rs2734648; hg19: chr3-46411840;