3-46370768-C-T

Variant names:

• chr3-46370768-C-T
• rs1799988
• NM_000579.4:c.-232C>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.-232C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,988 control chromosomes in the GnomAD database, including 18,629 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 0.49 (18629 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CCR5 NM_000579.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• Publications: 71 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR5	NM_001394783.1	c.-232C>T		upstream_gene_variant		ENST00000292303.5	NP_001381712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR5	ENST00000292303.5	c.-232C>T		upstream_gene_variant		1	NM_001394783.1	ENSP00000292303.4

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74711 AN: 151870 Hom.: 18608 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.492 AC: 74767 AN: 151988 Hom.: 18629 Cov.: 32 AF XY: 0.497 AC XY: 36897 AN XY: 74282

African (AFR) AF: 0.571 AC: 23657 AN: 41420

American (AMR) AF: 0.461 AC: 7034 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1539 AN: 3468

East Asian (EAS) AF: 0.590 AC: 3055 AN: 5176

South Asian (SAS) AF: 0.613 AC: 2951 AN: 4814

European-Finnish (FIN) AF: 0.463 AC: 4885 AN: 10544

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30016 AN: 67970

Other (OTH) AF: 0.491 AC: 1040 AN: 2116

Alfa AF: 0.459 Hom.: 4437

Bravo AF: 0.493

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.59
PhyloP100		-0.77
PromoterAI		0.0044	Neutral
Mutation Taster		=299/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1799988; hg19: chr3-46412259; COSMIC: COSV52753248;