rs41526948

chr3-46375195-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001394783.1(CCR5):c.*1234A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 167,182 control chromosomes in the GnomAD database, including 31 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 0.012 (22 hom., cov: 30)
  • Exomes 𝑓: 0.033 (9 hom.)
• Consequence: CCR5 NM_001394783.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0124 (1888/152246) while in subpopulation NFE AF= 0.017 (1156/68018). AF 95% confidence interval is 0.0162. There are 22 homozygotes in gnomad4. There are 1015 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1889 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR5	NM_001394783.1	c.*1234A>G		3_prime_UTR_variant	2/2	ENST00000292303.5
CCR5AS	NR_125406.1	n.392-3778T>C		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4	c.*1234A>G		3_prime_UTR_variant	3/3
CCR5	NM_001100168.2	c.*1234A>G		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR5	ENST00000292303.5	c.*1234A>G		3_prime_UTR_variant	2/2	1	NM_001394783.1	P1
CCR5AS	ENST00000701879.1	n.174-3778T>C		intron_variant, non_coding_transcript_variant
CCR5AS	ENST00000451485.2	n.392-3778T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1889 AN: 152128 Hom.: 22 Cov.: 30

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00988

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0101

GnomAD4 exome AF: 0.0331 AC: 494 AN: 14936 Hom.: 9 Cov.: 0 AF XY: 0.0341 AC XY: 242 AN XY: 7106

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0333

Gnomad4 NFE exome AF: 0.00794

Gnomad4 OTH exome AF: 0.0417

GnomAD4 genome AF: 0.0124 AC: 1888 AN: 152246 Hom.: 22 Cov.: 30 AF XY: 0.0136 AC XY: 1015 AN XY: 74440

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.00987

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0154

Gnomad4 FIN AF: 0.0313

Gnomad4 NFE AF: 0.0170

Gnomad4 OTH AF: 0.00995

Alfa AF: 0.0133 Hom.: 4

Bravo AF: 0.00991

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.52
Dann	Benign	0.54

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: rs41526948; hg19: chr3-46416686; COSMIC: COSV52752168; COSMIC: COSV52752168;