rs333

chr3-46373452-TACAGTCAGTATCAATTCTGGAAGAATTTCCAG-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PVS1_StrongBA1

The NM_001394783(CCR5):c.554_585del(p.Ser185IlefsTer32) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 152034 control chromosomes in the gnomAD Genomes database, including 553 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.072 ( 553 hom., cov: 31)

Exomes 𝑓: 0.074 ( 966 hom. )

Consequence

CCR5
NM_001394783 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:3O:2

Conservation

PhyloP100: 0.894

Links

CCR5 (HGNC:1606):

CCR5AS (HGNC:54398):

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Fraction of 0.48 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BA1

GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCR5	NM_001394783.1 linkuse as main transcript	c.554_585del	p.Ser185IlefsTer32	frameshift_variant	2/2	ENST00000292303.5
CCR5AS	NR_125406.1 linkuse as main transcript	n.392-2067_392-2036del		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4 linkuse as main transcript	c.554_585del	p.Ser185IlefsTer32	frameshift_variant	3/3
CCR5	NM_001100168.2 linkuse as main transcript	c.554_585del	p.Ser185IlefsTer32	frameshift_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCR5	ENST00000292303.5 linkuse as main transcript	c.554_585del	p.Ser185IlefsTer32	frameshift_variant	2/2	1	NM_001394783.1	P1
CCR5AS	ENST00000701879.1 linkuse as main transcript	n.174-2067_174-2036del		intron_variant, non_coding_transcript_variant
CCR5	ENST00000445772.1 linkuse as main transcript	c.554_585del	p.Ser185IlefsTer32	frameshift_variant	1/1			P1
CCR5AS	ENST00000451485.2 linkuse as main transcript	n.392-2067_392-2036del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0718

AC:

10911

AN:

152034

Hom.:

553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0204

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.0370

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.0483

GnomAD3 exomes

AF:

0.0743

AC:

18640

AN:

251006

Hom.:

966

AF XY:

0.0745

AC XY:

10108

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.0293

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0160

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.0726

GnomAD4 exome

AF:

0.100

AC:

146811

AN:

1461718

Hom.:

8315

AF XY:

0.0983

AC XY:

71450

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.0154

Gnomad4 AMR exome

AF:

0.0303

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0171

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.0877

Alfa

AF:

0.0929

Hom.:

121

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0915

EpiControl

AF:

0.0970

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 22, 2019

- -

Susceptibility to HIV infection

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Dec 01, 2008

- -

Resistance to hepatitis C virus

Benign:1

protective, no assertion criteria provided

literature only

OMIM

Dec 01, 2008

- -

West Nile virus, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 01, 2008

- -

Multiple sclerosis modifier of disease progression

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over