rs2254089

Positions:

• chr3-46371927-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+939C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,932 control chromosomes in the GnomAD database, including 7,809 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 (7809 hom., cov: 32)
• Consequence: CCR5 NM_001394783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR5	NM_001394783.1	c.-12+939C>T		intron_variant		ENST00000292303.5	NP_001381712.1
CCR5AS	NR_125406.1	n.392-510G>A		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4	c.-12+939C>T		intron_variant			NP_000570.1
CCR5	NM_001100168.2	c.-12+939C>T		intron_variant			NP_001093638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR5	ENST00000292303.5	c.-12+939C>T		intron_variant		1	NM_001394783.1	ENSP00000292303	P1
CCR5AS	ENST00000701879.1	n.174-510G>A		intron_variant, non_coding_transcript_variant
CCR5AS	ENST00000451485.2	n.392-510G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45654 AN: 151814 Hom.: 7808 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.301 AC: 45661 AN: 151932 Hom.: 7809 Cov.: 32 AF XY: 0.305 AC XY: 22613 AN XY: 74240

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.345

Alfa AF: 0.280 Hom.: 970

Bravo AF: 0.297

Asia WGS AF: 0.413 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.86
DANN	Benign	0.58

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: rs2254089; hg19: chr3-46413418;