chr3-46373205-T-A

Position:

chr3-46373205-T-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

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

Scores

Clinical Significance

protective no assertion criteria provided B:1

Conservation

PhyloP100: -2.00

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 Likely_benign. Variant got -5 ACMG points.

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 GnomAd4 at 129 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCR5	NM_001394783.1 linkuse as main transcript	c.303T>A	p.Cys101Ter	stop_gained	2/2	ENST00000292303.5	NP_001381712.1
CCR5AS	NR_125406.1 linkuse as main transcript	n.392-1788A>T		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4 linkuse as main transcript	c.303T>A	p.Cys101Ter	stop_gained	3/3		NP_000570.1
CCR5	NM_001100168.2 linkuse as main transcript	c.303T>A	p.Cys101Ter	stop_gained	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.303T>A	p.Cys101Ter	stop_gained	2/2	1	NM_001394783.1	ENSP00000292303	P1
CCR5AS	ENST00000701879.1 linkuse as main transcript	n.174-1788A>T		intron_variant, non_coding_transcript_variant
CCR5	ENST00000445772.1 linkuse as main transcript	c.303T>A	p.Cys101Ter	stop_gained	1/1			ENSP00000404881	P1
CCR5AS	ENST00000451485.2 linkuse as main transcript	n.392-1788A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000848

AC:

129

AN:

152204

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.000692

AC XY:

AN XY:

135840

show subpopulations

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.:

Cov.:

AF XY:

0.00149

AC XY:

1082

AN XY:

727242

show subpopulations

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.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74488

show subpopulations

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.:

Bravo

AF:

0.000797

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000931

AC:

ExAC

AF:

0.000585

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.00166

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

Jan 03, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.71

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.092

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

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