rs1800940

chr3-46373082-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_001394783.1(CCR5):c.180G>T(p.Arg60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,614,172 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (6 hom.)
• Consequence: CCR5 NM_001394783.1 missense
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: -0.429

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09222919).
• BP6: Variant 3-46373082-G-T is Benign according to our data. Variant chr3-46373082-G-T is described in ClinVar as [protective]. Clinvar id is 8191.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 168 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR5	NM_001394783.1	c.180G>T	p.Arg60Ser	missense_variant	2/2	ENST00000292303.5
CCR5AS	NR_125406.1	n.392-1665C>A		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4	c.180G>T	p.Arg60Ser	missense_variant	3/3
CCR5	NM_001100168.2	c.180G>T	p.Arg60Ser	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR5	ENST00000292303.5	c.180G>T	p.Arg60Ser	missense_variant	2/2	1	NM_001394783.1	P1
CCR5AS	ENST00000701879.1	n.174-1665C>A		intron_variant, non_coding_transcript_variant
CCR5	ENST00000445772.1	c.180G>T	p.Arg60Ser	missense_variant	1/1			P1
CCR5AS	ENST00000451485.2	n.392-1665C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 168 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00172

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000923 AC: 232 AN: 251390 Hom.: 1 AF XY: 0.00105 AC XY: 142 AN XY: 135862

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000954

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00157

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00168 AC: 2453 AN: 1461876 Hom.: 6 Cov.: 32 AF XY: 0.00161 AC XY: 1169 AN XY: 727242

Gnomad4 AFR exome AF: 0.000448

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.00206

Gnomad4 OTH exome AF: 0.00123

GnomAD4 genome AF: 0.00110 AC: 168 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.00101 AC XY: 75 AN XY: 74470

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00172

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00129 Hom.: 1

Bravo AF: 0.00115

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.000725 AC: 88

EpiCase AF: 0.00180

EpiControl AF: 0.00219

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

Jun 01, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	16
Dann	Uncertain	0.98
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.21	N
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.000067	A;A;A
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.4	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.058	T;T
Polyphen		0.079	B;B
Vest4		0.14
MutPred		0.36		Loss of ubiquitination at K59 (P = 0.1557);Loss of ubiquitination at K59 (P = 0.1557);
MVP		0.58
ClinPred		0.044	T
GERP RS		4.5
Varity_R		0.66
gMVP		0.31

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: rs1800940; hg19: chr3-46414573; COSMIC: COSV99433796;