chr3-46373570-G-A

Position:

chr3-46373570-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001394783.1(CCR5):c.668G>A(p.Arg223Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,613,554 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 93 hom. )

Consequence

CCR5
NM_001394783.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.179

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027464628).

BP6

Variant 3-46373570-G-A is Benign according to our data. Variant chr3-46373570-G-A is described in ClinVar as [Benign]. Clinvar id is 8186.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCR5	NM_001394783.1 linkuse as main transcript	c.668G>A	p.Arg223Gln	missense_variant	2/2	ENST00000292303.5	NP_001381712.1
CCR5AS	NR_125406.1 linkuse as main transcript	n.392-2153C>T		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4 linkuse as main transcript	c.668G>A	p.Arg223Gln	missense_variant	3/3		NP_000570.1
CCR5	NM_001100168.2 linkuse as main transcript	c.668G>A	p.Arg223Gln	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.668G>A	p.Arg223Gln	missense_variant	2/2	1	NM_001394783.1	ENSP00000292303	P1
CCR5AS	ENST00000701879.1 linkuse as main transcript	n.174-2153C>T		intron_variant, non_coding_transcript_variant
CCR5	ENST00000445772.1 linkuse as main transcript	c.668G>A	p.Arg223Gln	missense_variant	1/1			ENSP00000404881	P1
CCR5AS	ENST00000451485.2 linkuse as main transcript	n.392-2153C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

412

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.0514

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00492

AC:

1235

AN:

250954

Hom.:

AF XY:

0.00461

AC XY:

625

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00538

Gnomad EAS exome

AF:

0.0526

Gnomad SAS exome

AF:

0.00229

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.000978

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00275

AC:

4021

AN:

1461360

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

2025

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00563

Gnomad4 EAS exome

AF:

0.0615

Gnomad4 SAS exome

AF:

0.00262

Gnomad4 FIN exome

AF:

0.000468

Gnomad4 NFE exome

AF:

0.000888

Gnomad4 OTH exome

AF:

0.00277

GnomAD4 genome

AF:

0.00272

AC:

414

AN:

152194

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

225

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.0521

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00244

Hom.:

Bravo

AF:

0.00326

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00502

AC:

610

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00136

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CCR5 POLYMORPHISM, ORIENTAL 2

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jul 01, 1997

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.76

.;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.073

Sift

Benign

0.064

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.066

B;B

Vest4

0.044

MVP

0.41

ClinPred

0.031

GERP RS

4.8

Varity_R

0.37

gMVP

0.37

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