chr3-46370170-A-G

Position:

• chr3-46370170-A-G

Variant summary

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

The NM_000579.4(CCR5):​c.-329A>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 0.109 in 152,206 control chromosomes in the GnomAD database, including 1,099 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 0.11 (1099 hom., cov: 31)
• Consequence: CCR5 NM_000579.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR5	NM_000579.4	c.-329A>G		5_prime_UTR_variant	1/3		NP_000570.1
CCR5	NM_001100168.2	c.-94A>G		5_prime_UTR_variant	1/3		NP_001093638.1
CCR5AS	NR_125406.2	n.572+1074T>C		intron_variant
CCR5AS	NR_185891.1	n.344+1074T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR5AS	ENST00000451485.2	n.565+1074T>C		intron_variant		3
CCR5AS	ENST00000701879.1	n.347+1074T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16542 AN: 152088 Hom.: 1099 Cov.: 31

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.0824

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.109 AC: 16550 AN: 152206 Hom.: 1099 Cov.: 31 AF XY: 0.106 AC XY: 7864 AN XY: 74412

Gnomad4 AFR AF: 0.0615

Gnomad4 AMR AF: 0.0825

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0236

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.132 Hom.: 311

Bravo AF: 0.102

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2856758; hg19: chr3-46411661;