chr3-46372528-CACA-C

Position:

• chr3-46372528-CACA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001394783.1(CCR5):​c.-11-344_-11-342del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 167,440 control chromosomes in the GnomAD database, including 8,282 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7686 hom., cov: 0)
  • Exomes 𝑓: 0.26 (596 hom.)
• Consequence: CCR5 NM_001394783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR5	NM_001394783.1	c.-11-344_-11-342del		intron_variant		ENST00000292303.5	NP_001381712.1
CCR5AS	NR_125406.1	n.392-1114_392-1112del		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4	c.-11-344_-11-342del		intron_variant			NP_000570.1
CCR5	NM_001100168.2	c.-11-344_-11-342del		intron_variant			NP_001093638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR5	ENST00000292303.5	c.-11-344_-11-342del		intron_variant		1	NM_001394783.1	ENSP00000292303	P1
CCR5AS	ENST00000701879.1	n.174-1114_174-1112del		intron_variant, non_coding_transcript_variant
CCR5AS	ENST00000451485.2	n.392-1114_392-1112del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45327 AN: 151276 Hom.: 7685 Cov.: 0

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.260 AC: 4167 AN: 16046 Hom.: 596 AF XY: 0.256 AC XY: 2382 AN XY: 9296

Gnomad4 AFR exome AF: 0.0698

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.409

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.299 AC: 45334 AN: 151394 Hom.: 7686 Cov.: 0 AF XY: 0.304 AC XY: 22439 AN XY: 73918

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.344

Bravo AF: 0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs71619644; hg19: chr3-46414019;