rs41515644

Positions:

• chr3-46372544-A-G

Variant summary

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

The NM_001394783.1(CCR5):​c.-11-348A>G 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 170,364 control chromosomes in the GnomAD database, including 8,490 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 0.30 (7716 hom., cov: 31)
  • Exomes 𝑓: 0.27 (774 hom.)
• Consequence: CCR5 NM_001394783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR5	NM_001394783.1	c.-11-348A>G		intron_variant		ENST00000292303.5
CCR5AS	NR_125406.1	n.392-1127T>C		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4	c.-11-348A>G		intron_variant
CCR5	NM_001100168.2	c.-11-348A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR5	ENST00000292303.5	c.-11-348A>G		intron_variant		1	NM_001394783.1	P1
CCR5AS	ENST00000701879.1	n.174-1127T>C		intron_variant, non_coding_transcript_variant
CCR5AS	ENST00000451485.2	n.392-1127T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45458 AN: 151644 Hom.: 7715 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.266 AC: 4942 AN: 18602 Hom.: 774 AF XY: 0.261 AC XY: 2776 AN XY: 10632

Gnomad4 AFR exome AF: 0.0812

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.300 AC: 45465 AN: 151762 Hom.: 7716 Cov.: 31 AF XY: 0.304 AC XY: 22522 AN XY: 74150

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.345

Alfa AF: 0.290 Hom.: 769

Asia WGS AF: 0.412 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.16

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: rs41515644; hg19: chr3-46414035;