rs1800023

Variant names:

• chr3-46370817-A-G
• rs1800023
• ENST00000451485.3:n.572+427T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-46370817-A-G
• chr3-46370817-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000579.4(CCR5):​c.-183A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,144 control chromosomes in the GnomAD database, including 7,819 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 (7819 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CCR5 NM_000579.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 40 publications found

Genes affected

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

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000579.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5AS	NR_125406.2	MANE Select	n.572+427T>C		intron	N/A
	CCR5	NM_000579.4		c.-183A>G		5_prime_UTR	Exon 2 of 3	NP_000570.1	Q38L21
	CCR5	NM_001100168.2		c.-65-118A>G		intron	N/A	NP_001093638.1	Q38L21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5AS	ENST00000451485.3	TSL:3 MANE Select	n.572+427T>C		intron	N/A
	CCR5AS	ENST00000701879.2		n.462+427T>C		intron	N/A
	CCR5AS	ENST00000717843.1		n.324+427T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45701 AN: 152026 Hom.: 7818 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.349

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.300 AC: 45708 AN: 152144 Hom.: 7819 Cov.: 32 AF XY: 0.305 AC XY: 22648 AN XY: 74374

African (AFR) AF: 0.127 AC: 5288 AN: 41548

American (AMR) AF: 0.376 AC: 5748 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1329 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2879 AN: 5176

South Asian (SAS) AF: 0.416 AC: 2005 AN: 4822

European-Finnish (FIN) AF: 0.307 AC: 3239 AN: 10564

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.354 AC: 24058 AN: 67974

Other (OTH) AF: 0.346 AC: 733 AN: 2116

Alfa AF: 0.258 Hom.: 1913

Bravo AF: 0.297

Asia WGS AF: 0.412 AC: 1433 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.4
DANN	Benign	0.63
PhyloP100		0.27
PromoterAI		0.040	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1800023; hg19: chr3-46412308;