rs1800024

Positions:

• chr3-46371068-C-T

Variant summary

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

The NM_001394783.1(CCR5):​c.-12+80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,192 control chromosomes in the GnomAD database, including 1,566 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 0.13 (1566 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CCR5 NM_001394783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

Genes affected

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR5	NM_001394783.1	c.-12+80C>T		intron_variant		ENST00000292303.5
CCR5AS	NR_125406.1	n.565+176G>A		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4	c.-12+80C>T		intron_variant
CCR5	NM_001100168.2	c.-12+80C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR5	ENST00000292303.5	c.-12+80C>T		intron_variant		1	NM_001394783.1	P1
CCR5AS	ENST00000701879.1	n.347+176G>A		intron_variant, non_coding_transcript_variant
CCR5AS	ENST00000451485.2	n.565+176G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20171 AN: 152072 Hom.: 1561 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0635

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.133 AC: 20201 AN: 152190 Hom.: 1566 Cov.: 32 AF XY: 0.134 AC XY: 9939 AN XY: 74416

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0635

Gnomad4 NFE AF: 0.0904

Gnomad4 OTH AF: 0.137

Alfa AF: 0.131 Hom.: 214

Bravo AF: 0.145

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800024; hg19: chr3-46412559;