3-46370349-G-T

Variant names:

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

Variant summary

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

The ENST00000451485.3(CCR5AS):​n.572+895C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 149,894 control chromosomes in the GnomAD database, including 9,899 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 0.36 (9899 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5AS	NR_125406.2	MANE Select	n.572+895C>A		intron	N/A
	CCR5	NM_000579.4		c.-301+151G>T		intron	N/A	NP_000570.1
	CCR5	NM_001100168.2		c.-66+151G>T		intron	N/A	NP_001093638.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5AS	ENST00000451485.3	TSL:3 MANE Select	n.572+895C>A		intron	N/A
	CCR5AS	ENST00000701879.2		n.462+895C>A		intron	N/A
	CCR5AS	ENST00000717843.1		n.324+895C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.365 AC: 54594 AN: 149774 Hom.: 9896 Cov.: 29

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.364 AC: 54613 AN: 149894 Hom.: 9899 Cov.: 29 AF XY: 0.366 AC XY: 26783 AN XY: 73152

African (AFR) AF: 0.343 AC: 13982 AN: 40800

American (AMR) AF: 0.397 AC: 5988 AN: 15068

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1327 AN: 3446

East Asian (EAS) AF: 0.564 AC: 2849 AN: 5054

South Asian (SAS) AF: 0.423 AC: 1988 AN: 4700

European-Finnish (FIN) AF: 0.319 AC: 3184 AN: 9986

Middle Eastern (MID) AF: 0.448 AC: 129 AN: 288

European-Non Finnish (NFE) AF: 0.356 AC: 24055 AN: 67574

Other (OTH) AF: 0.388 AC: 807 AN: 2080

Alfa AF: 0.340 Hom.: 2143

Bravo AF: 0.367

Asia WGS AF: 0.425 AC: 1479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.56
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism (auto)

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;