3-46372528-CACAACA-C

Variant names:

• chr3-46372528-CACAACA-C
• rs71619644
• NM_001394783.1:c.-11-347_-11-342delCAACAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001394783.1(CCR5):​c.-11-347_-11-342delCAACAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 16,470 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: CCR5 NM_001394783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR5	NM_001394783.1	c.-11-347_-11-342delCAACAA		intron_variant	Intron 1 of 1	ENST00000292303.5	NP_001381712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR5	ENST00000292303.5	c.-11-363_-11-358delACAACA		intron_variant	Intron 1 of 1	1	NM_001394783.1	ENSP00000292303.4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.000182 AC: 3 AN: 16470 Hom.: 0 AF XY: 0.000210 AC XY: 2 AN XY: 9542

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 268

American (AMR) AF: 0.00 AC: 0 AN: 1808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 234

East Asian (EAS) AF: 0.00 AC: 0 AN: 530

South Asian (SAS) AF: 0.00 AC: 0 AN: 1348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 34

European-Non Finnish (NFE) AF: 0.000270 AC: 3 AN: 11102

Other (OTH) AF: 0.00 AC: 0 AN: 700

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs71619644; hg19: chr3-46414019;