dbSNP rs34171309: CCL3:p.Glu78Asp (chr17-36088717-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002983.3(CCL3):c.234G>T(p.Glu78Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,613,780 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 160 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 151 hom. )

Consequence

CCL3
NM_002983.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.98

Publications

6 publications found

Variant links:

Genes affected

CCL3 (HGNC:10627): (C-C motif chemokine ligand 3) This locus represents a small inducible cytokine. The encoded protein, also known as macrophage inflammatory protein 1 alpha, plays a role in inflammatory responses through binding to the receptors CCR1, CCR4 and CCR5. Polymorphisms at this locus may be associated with both resistance and susceptibility to infection by human immunodeficiency virus type 1.[provided by RefSeq, Sep 2010]

CCL3 links:

CCL3-AS1 (HGNC:55229): (CCL3 antisense RNA 1)

CCL3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017627776).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL3	NM_002983.3 link	c.234G>T	p.Glu78Asp	missense_variant	Exon 3 of 3	ENST00000613922.2	NP_002974.1	P10147A0N0R1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL3	ENST00000613922.2 link	c.234G>T	p.Glu78Asp	missense_variant	Exon 3 of 3	1	NM_002983.3	ENSP00000477908.1		P10147

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3699

AN:

152078

Hom.:

155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0783

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00194

Gnomad OTH

AF:

0.0272

GnomAD2 exomes

AF:

0.00808

AC:

2030

AN:

251206

AF XY:

0.00651

show subpopulations

Gnomad AFR exome

AF:

0.0826

Gnomad AMR exome

AF:

0.00980

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00225

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00403

AC:

5886

AN:

1461584

Hom.:

151

Cov.:

AF XY:

0.00374

AC XY:

2717

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.0805

AC:

2695

AN:

33466

American (AMR)

AF:

0.0107

AC:

478

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00191

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000162

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0193

AC:

110

AN:

5688

European-Non Finnish (NFE)

AF:

0.00176

AC:

1956

AN:

1111848

Other (OTH)

AF:

0.00964

AC:

582

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

348

697

1045

1394

1742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0244

AC:

3715

AN:

152196

Hom.:

160

Cov.:

AF XY:

0.0246

AC XY:

1831

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0785

AC:

3255

AN:

41484

American (AMR)

AF:

0.0167

AC:

256

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000831

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00196

AC:

133

AN:

68030

Other (OTH)

AF:

0.0270

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

159

318

476

635

794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.0282

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0865

AC:

381

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00941

AC:

1142

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.73

CADD

Benign

3.1

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.046

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.058

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.91

PhyloP100

-2.0

PrimateAI

Benign

0.34

Sift4G

Benign

0.75

Polyphen

0.0010

Vest4

0.11

MutPred

0.12

Loss of catalytic residue at W80 (P = 0.0511);

MVP

0.40

ClinPred

0.0035

GERP RS

1.3

Varity_R

0.35

gMVP

0.30

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over