3-46372528-CACAACAACA-CACAACAACAACA

Variant names:

• chr3-46372528-C-CACA
• rs71619644
• NM_001394783.1:c.-11-344_-11-342dupCAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001394783.1(CCR5):​c.-11-344_-11-342dupCAA 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 NM_001394783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 1 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 -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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1017 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394783.1. 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
	CCR5	NM_001394783.1	MANE Select	c.-11-344_-11-342dupCAA		intron	N/A	NP_001381712.1	Q38L21
	CCR5AS	NR_125406.2	MANE Select	n.399-1114_399-1112dupTGT		intron	N/A
	CCR5	NM_000579.4		c.-11-344_-11-342dupCAA		intron	N/A	NP_000570.1	Q38L21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5	ENST00000292303.5	TSL:1 MANE Select	c.-11-364_-11-363insACA		intron	N/A	ENSP00000292303.4	P51681
	CCR5AS	ENST00000451485.3	TSL:3 MANE Select	n.399-1112_399-1111insTGT		intron	N/A
	CCR5AS	ENST00000701879.2		n.289-1112_289-1111insTGT		intron	N/A

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

African (AFR) AF: 0.0112 AC: 3 AN: 268

American (AMR) AF: 0.00 AC: 0 AN: 1808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 234

East Asian (EAS) AF: 0.00 AC: 0 AN: 530

South Asian (SAS) AF: 0.00 AC: 0 AN: 1350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 34

European-Non Finnish (NFE) AF: 0.000180 AC: 2 AN: 11100

Other (OTH) AF: 0.00287 AC: 2 AN: 698

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

African (AFR) AF: 0.0233 AC: 964 AN: 41386

American (AMR) AF: 0.00197 AC: 30 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67806

Other (OTH) AF: 0.00382 AC: 8 AN: 2092

Alfa AF: 0.000179 Hom.: 170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71619644; hg19: chr3-46414019;