rs1800560

chr3-46373205-T-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM4 BP6 BS2

The NM_001394783.1(CCR5):c.303T>A(p.Cys101Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,614,194 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

• Frequency:
  • Genomes: 𝑓 0.00085 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (4 hom.)
• Consequence: CCR5 NM_001394783.1 stop_gained
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: -2.00

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 Likely_benign. Variant got -3 ACMG points.

• PM4: Stoplost variant in NM_001394783.1 Downstream stopcodon found after 370 codons.
• BP6: Variant 3-46373205-T-A is Benign according to our data. Variant chr3-46373205-T-A is described in ClinVar as [protective]. Clinvar id is 8188.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective].
• BS2: High AC in GnomAd at 129 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR5	NM_001394783.1	c.303T>A	p.Cys101Ter	stop_gained	2/2	ENST00000292303.5
CCR5AS	NR_125406.1	n.392-1788A>T		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4	c.303T>A	p.Cys101Ter	stop_gained	3/3
CCR5	NM_001100168.2	c.303T>A	p.Cys101Ter	stop_gained	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR5	ENST00000292303.5	c.303T>A	p.Cys101Ter	stop_gained	2/2	1	NM_001394783.1	P1
CCR5AS	ENST00000701879.1	n.174-1788A>T		intron_variant, non_coding_transcript_variant
CCR5	ENST00000445772.1	c.303T>A	p.Cys101Ter	stop_gained	1/1			P1
CCR5AS	ENST00000451485.2	n.392-1788A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000848 AC: 129 AN: 152204 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

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: 0.00141

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000633 AC: 159 AN: 251356 Hom.: 1 AF XY: 0.000692 AC XY: 94 AN XY: 135840

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00122

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00156 AC: 2274 AN: 1461872 Hom.: 4 Cov.: 32 AF XY: 0.00149 AC XY: 1082 AN XY: 727242

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00196

Gnomad4 OTH exome AF: 0.00116

GnomAD4 genome AF: 0.000847 AC: 129 AN: 152322 Hom.: 2 Cov.: 32 AF XY: 0.000846 AC XY: 63 AN XY: 74488

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.000797

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000931 AC: 8

ExAC AF: 0.000585 AC: 71

EpiCase AF: 0.000927

EpiControl AF: 0.00166

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Susceptibility to HIV infection Benign:1

protective, no assertion criteria provided

literature only

OMIM

Jan 03, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	21
Dann	Benign	0.95
Eigen	Benign	-0.71
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.092	N
MutationTaster	Benign	1.0	A;A;A
Vest4		0.92
GERP RS		-11

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: rs1800560; hg19: chr3-46414696; COSMIC: COSV99433048;