chr3-46372528-C-CACA

Position:

• chr3-46372528-C-CACA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000292303.5(CCR5):​c.-11-344_-11-342dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 168,008 control chromosomes in the GnomAD database, including 12 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0067 (12 hom., cov: 0)
  • Exomes 𝑓: 0.00043 (0 hom.)
• Consequence: CCR5 ENST00000292303.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00671 (1017/151540) while in subpopulation AFR AF= 0.0233 (964/41386). AF 95% confidence interval is 0.0221. There are 12 homozygotes in gnomad4. There are 468 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1017 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR5	NM_001394783.1	c.-11-344_-11-342dup		intron_variant		ENST00000292303.5	NP_001381712.1
CCR5AS	NR_125406.1	n.392-1112_392-1111insTGT		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4	c.-11-344_-11-342dup		intron_variant			NP_000570.1
CCR5	NM_001100168.2	c.-11-344_-11-342dup		intron_variant			NP_001093638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR5	ENST00000292303.5	c.-11-344_-11-342dup		intron_variant		1	NM_001394783.1	ENSP00000292303	P1
CCR5AS	ENST00000701879.1	n.174-1112_174-1111insTGT		intron_variant, non_coding_transcript_variant
CCR5AS	ENST00000451485.2	n.392-1112_392-1111insTGT		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00672 AC: 1017 AN: 151422 Hom.: 12 Cov.: 0

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00386

GnomAD4 exome AF: 0.000425 AC: 7 AN: 16468 Hom.: 0 AF XY: 0.000524 AC XY: 5 AN XY: 9542

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000180

Gnomad4 OTH exome AF: 0.00287

GnomAD4 genome AF: 0.00671 AC: 1017 AN: 151540 Hom.: 12 Cov.: 0 AF XY: 0.00632 AC XY: 468 AN XY: 74018

Gnomad4 AFR AF: 0.0233

Gnomad4 AMR AF: 0.00197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00382

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71619644; hg19: chr3-46414019;