Genetic Variant CCL3:c.74-303C>T (chr17-36089600-G-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.74-303C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 606,860 control chromosomes in the GnomAD database, including 16,281 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 0.20 ( 3380 hom., cov: 31)

Exomes 𝑓: 0.23 ( 12901 hom. )

Consequence

CCL3
NM_002983.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0790

Publications

18 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002983.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCL3	NM_002983.3	MANE Select	c.74-303C>T	intron	N/A	NP_002974.1	P10147
CCL3	NR_168494.1		n.544C>T	non_coding_transcript_exon	Exon 1 of 2
CCL3-AS1	NR_186417.1		n.384G>A	non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCL3	ENST00000613922.2	TSL:1 MANE Select	c.74-303C>T	intron	N/A	ENSP00000477908.1	P10147
CCL3	ENST00000614051.1	TSL:1	n.570C>T	non_coding_transcript_exon	Exon 1 of 2
CCL3	ENST00000613928.1	TSL:5	n.535C>T	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30883

AN:

151946

Hom.:

3376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.233

AC:

105902

AN:

454796

Hom.:

12901

Cov.:

AF XY:

0.234

AC XY:

57408

AN XY:

245696

show subpopulations

African (AFR)

AF:

0.135

AC:

1719

AN:

12728

American (AMR)

AF:

0.207

AC:

4359

AN:

21074

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

2773

AN:

14322

East Asian (EAS)

AF:

0.322

AC:

9177

AN:

28472

South Asian (SAS)

AF:

0.228

AC:

11071

AN:

48552

European-Finnish (FIN)

AF:

0.168

AC:

4643

AN:

27672

Middle Eastern (MID)

AF:

0.191

AC:

384

AN:

2008

European-Non Finnish (NFE)

AF:

0.241

AC:

66000

AN:

274096

Other (OTH)

AF:

0.223

AC:

5776

AN:

25872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

4155

8310

12466

16621

20776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.203

AC:

30890

AN:

152064

Hom.:

3380

Cov.:

AF XY:

0.201

AC XY:

14947

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.134

AC:

5569

AN:

41474

American (AMR)

AF:

0.200

AC:

3062

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

605

AN:

3472

East Asian (EAS)

AF:

0.344

AC:

1777

AN:

5164

South Asian (SAS)

AF:

0.237

AC:

1138

AN:

4808

European-Finnish (FIN)

AF:

0.156

AC:

1648

AN:

10582

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.240

AC:

16314

AN:

67956

Other (OTH)

AF:

0.205

AC:

433

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1225

2450

3675

4900

6125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.221

Hom.:

626

Bravo

AF:

0.207

Asia WGS

AF:

0.310

AC:

1078

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.48

PhyloP100

0.079

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over