Genetic Variant NM_002983.3:c.189-43T>G (chr17-36088805-A-C) – 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.189-43T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,610,366 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts 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 ( 131 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 139 hom. )

Consequence

CCL3
NM_002983.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00300

Publications

4 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 (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL3	NM_002983.3 link	c.189-43T>G		intron_variant	Intron 2 of 2	ENST00000613922.2	NP_002974.1	P10147A0N0R1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL3	ENST00000613922.2 link	c.189-43T>G		intron_variant	Intron 2 of 2	1	NM_002983.3	ENSP00000477908.1		P10147

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

3610

AN:

152178

Hom.:

129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0805

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.0205

GnomAD2 exomes

AF:

0.00750

AC:

1879

AN:

250692

AF XY:

0.00590

show subpopulations

Gnomad AFR exome

AF:

0.0846

Gnomad AMR exome

AF:

0.00784

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000486

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00316

AC:

4606

AN:

1458070

Hom.:

139

Cov.:

AF XY:

0.00302

AC XY:

2193

AN XY:

725562

show subpopulations

African (AFR)

AF:

0.0853

AC:

2848

AN:

33382

American (AMR)

AF:

0.00837

AC:

374

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26104

East Asian (EAS)

AF:

0.000126

AC:

AN:

39688

South Asian (SAS)

AF:

0.00443

AC:

382

AN:

86184

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00548

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.000523

AC:

580

AN:

1108724

Other (OTH)

AF:

0.00626

AC:

377

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

264

528

791

1055

1319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.0238

AC:

3623

AN:

152296

Hom.:

131

Cov.:

AF XY:

0.0233

AC XY:

1736

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0805

AC:

3346

AN:

41550

American (AMR)

AF:

0.0103

AC:

157

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3462

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.00415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000764

AC:

AN:

68024

Other (OTH)

AF:

0.0203

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

167

333

500

666

833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0101

Hom.:

Bravo

AF:

0.0275

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.8

(source)

DANN

Benign

0.75

PhyloP100

0.0030

Mutation Taster

=100/0

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