3-46372528-CACAACAACA-CACAACA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001394783.1(CCR5):​c.-11-344_-11-342delCAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 167,440 control chromosomes in the GnomAD database, including 8,282 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7686 hom., cov: 0)
  • Exomes 𝑓: 0.26 (596 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.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

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_-11-342delCAA		intron	N/A	NP_001381712.1	Q38L21
	CCR5AS	NR_125406.2	MANE Select	n.399-1114_399-1112delTGT		intron	N/A
	CCR5	NM_000579.4		c.-11-344_-11-342delCAA		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.-11-363_-11-361delACA		intron	N/A	ENSP00000292303.4	P51681
	CCR5AS	ENST00000451485.3	TSL:3 MANE Select	n.399-1114_399-1112delTGT		intron	N/A
	CCR5AS	ENST00000701879.2		n.289-1114_289-1112delTGT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45327 AN: 151276 Hom.: 7685 Cov.: 0

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.260 AC: 4167 AN: 16046 Hom.: 596 AF XY: 0.256 AC XY: 2382 AN XY: 9296

African (AFR) AF: 0.0698 AC: 18 AN: 258

American (AMR) AF: 0.313 AC: 551 AN: 1758

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 53 AN: 230

East Asian (EAS) AF: 0.409 AC: 212 AN: 518

South Asian (SAS) AF: 0.307 AC: 407 AN: 1326

European-Finnish (FIN) AF: 0.165 AC: 72 AN: 436

Middle Eastern (MID) AF: 0.500 AC: 15 AN: 30

European-Non Finnish (NFE) AF: 0.245 AC: 2651 AN: 10804

Other (OTH) AF: 0.274 AC: 188 AN: 686

GnomAD4 genome AF: 0.299 AC: 45334 AN: 151394 Hom.: 7686 Cov.: 0 AF XY: 0.304 AC XY: 22439 AN XY: 73918

African (AFR) AF: 0.127 AC: 5239 AN: 41352

American (AMR) AF: 0.376 AC: 5728 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1323 AN: 3466

East Asian (EAS) AF: 0.551 AC: 2801 AN: 5080

South Asian (SAS) AF: 0.415 AC: 1985 AN: 4782

European-Finnish (FIN) AF: 0.306 AC: 3195 AN: 10428

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23923 AN: 67766

Other (OTH) AF: 0.344 AC: 719 AN: 2088

Alfa AF: 0.108 Hom.: 170

Bravo AF: 0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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

Other links and lift over

dbSNP: rs71619644; hg19: chr3-46414019;