rs41515644

Variant names:

• chr3-46372544-A-G
• rs41515644
• NM_001394783.1:c.-11-348A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394783.1(CCR5):​c.-11-348A>G 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 170,364 control chromosomes in the GnomAD database, including 8,490 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 0.30 (7716 hom., cov: 31)
  • Exomes 𝑓: 0.27 (774 hom.)
• Consequence: CCR5 NM_001394783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5	NM_001394783.1	MANE Select	c.-11-348A>G		intron	N/A	NP_001381712.1
	CCR5AS	NR_125406.2	MANE Select	n.399-1127T>C		intron	N/A
	CCR5	NM_000579.4		c.-11-348A>G		intron	N/A	NP_000570.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR5	ENST00000292303.5	TSL:1 MANE Select	c.-11-348A>G		intron	N/A	ENSP00000292303.4
	CCR5AS	ENST00000451485.3	TSL:3 MANE Select	n.399-1127T>C		intron	N/A
	CCR5AS	ENST00000701879.2		n.289-1127T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45458 AN: 151644 Hom.: 7715 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.266 AC: 4942 AN: 18602 Hom.: 774 AF XY: 0.261 AC XY: 2776 AN XY: 10632

African (AFR) AF: 0.0812 AC: 25 AN: 308

American (AMR) AF: 0.315 AC: 612 AN: 1940

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 76 AN: 312

East Asian (EAS) AF: 0.431 AC: 274 AN: 636

South Asian (SAS) AF: 0.317 AC: 478 AN: 1508

European-Finnish (FIN) AF: 0.180 AC: 93 AN: 518

Middle Eastern (MID) AF: 0.440 AC: 22 AN: 50

European-Non Finnish (NFE) AF: 0.250 AC: 3124 AN: 12494

Other (OTH) AF: 0.285 AC: 238 AN: 836

GnomAD4 genome AF: 0.300 AC: 45465 AN: 151762 Hom.: 7716 Cov.: 31 AF XY: 0.304 AC XY: 22522 AN XY: 74150

African (AFR) AF: 0.127 AC: 5272 AN: 41468

American (AMR) AF: 0.376 AC: 5738 AN: 15244

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

East Asian (EAS) AF: 0.554 AC: 2824 AN: 5100

South Asian (SAS) AF: 0.414 AC: 1988 AN: 4802

European-Finnish (FIN) AF: 0.306 AC: 3217 AN: 10518

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

European-Non Finnish (NFE) AF: 0.353 AC: 23953 AN: 67860

Other (OTH) AF: 0.345 AC: 727 AN: 2106

Alfa AF: 0.290 Hom.: 769

Asia WGS AF: 0.412 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.16
PhyloP100		0.52
PromoterAI		-0.0091	Neutral
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: rs41515644; hg19: chr3-46414035;