Variant 3-46370444-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000579.4(CCR5):c.-301+246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,794 control chromosomes in the GnomAD database, including 18,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity,protective (no stars).

Frequency

Genomes: 𝑓 0.49 ( 18573 hom., cov: 30)

Consequence

CCR5
NM_000579.4 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity; protective no assertion criteria provided P:1B:3

Conservation

PhyloP100: -0.587

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
CCR5	NM_000579.4 link	c.-301+246A>G	intron_variant	Intron 1 of 2	NP_000570.1	P51681Q38L21
CCR5	NM_001100168.2 link	c.-66+246A>G	intron_variant	Intron 1 of 2	NP_001093638.1	P51681Q38L21
CCR5AS	NR_125406.2 link	n.572+800T>C	intron_variant	Intron 3 of 3
CCR5AS	NR_185891.1 link	n.344+800T>C	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR5AS	ENST00000451485.2 link	n.565+800T>C		intron_variant	Intron 3 of 3	3
CCR5AS	ENST00000701879.1 link	n.347+800T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74529

AN:

151674

Hom.:

18552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.571

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.460

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.441

Gnomad OTH

AF:

0.496

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.491

AC:

74586

AN:

151794

Hom.:

18573

Cov.:

AF XY:

0.496

AC XY:

36779

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.571

Gnomad4 AMR

AF:

0.460

Gnomad4 ASJ

AF:

0.444

Gnomad4 EAS

AF:

0.588

Gnomad4 SAS

AF:

0.612

Gnomad4 FIN

AF:

0.460

Gnomad4 NFE

AF:

0.441

Gnomad4 OTH

AF:

0.492

Alfa

AF:

0.458

Hom.:

3595

Bravo

AF:

0.493

Asia WGS

AF:

0.535

AC:

1859

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity; protective

Submissions summary: Pathogenic:1Benign:3

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Acquired immunodeficiency syndrome, delayed progression to

Pathogenic:1

Mar 01, 2003

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

CCR5-related disorder

Benign:1

Feb 18, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Susceptibility to HIV infection

Benign:1

Jul 08, 2003

OMIM

Significance: protective

Review Status: no assertion criteria provided

Collection Method: literature only

- -

CCR5 PROMOTER POLYMORPHISM

Benign:1

Jul 08, 2003

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.98

DANN

Benign

0.40

Splicing

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