chr3-46373082-G-T

Position:

chr3-46373082-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

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

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: -0.429

Variant links:

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]

CCR5 links:

CCR5AS (HGNC:54398): (CCR5 antisense RNA)

CCR5AS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 168 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCR5	NM_001394783.1 linkuse as main transcript	c.180G>T	p.Arg60Ser	missense_variant	2/2	ENST00000292303.5	NP_001381712.1
CCR5AS	NR_125406.1 linkuse as main transcript	n.392-1665C>A		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4 linkuse as main transcript	c.180G>T	p.Arg60Ser	missense_variant	3/3		NP_000570.1
CCR5	NM_001100168.2 linkuse as main transcript	c.180G>T	p.Arg60Ser	missense_variant	3/3		NP_001093638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCR5	ENST00000292303.5 linkuse as main transcript	c.180G>T	p.Arg60Ser	missense_variant	2/2	1	NM_001394783.1	ENSP00000292303	P1
CCR5AS	ENST00000701879.1 linkuse as main transcript	n.174-1665C>A		intron_variant, non_coding_transcript_variant
CCR5	ENST00000445772.1 linkuse as main transcript	c.180G>T	p.Arg60Ser	missense_variant	1/1			ENSP00000404881	P1
CCR5AS	ENST00000451485.2 linkuse as main transcript	n.392-1665C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

168

AN:

152178

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00105

AC XY:

142

AN XY:

135862

show subpopulations

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.:

Cov.:

AF XY:

0.00161

AC XY:

1169

AN XY:

727242

show subpopulations

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.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74470

show subpopulations

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.:

Bravo

AF:

0.00115

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000725

AC:

EpiCase

AF:

0.00180

EpiControl

AF:

0.00219

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

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

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.89

.;D

M_CAP

Benign

0.042

MetaRNN

Benign

0.092

T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.000067

A;A;A

PrimateAI

Benign

0.34

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over