rs1130371

Positions:

• chr17-36089191-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002983.3(CCL3):​c.180C>T​(p.Pro60Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,611,796 control chromosomes in the GnomAD database, including 40,944 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 (3360 hom., cov: 32)
  • Exomes 𝑓: 0.23 (37584 hom.)
• Consequence: CCL3 NM_002983.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.32

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

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-8.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL3	NM_002983.3	c.180C>T	p.Pro60Pro	synonymous_variant	2/3	ENST00000613922.2	NP_002974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL3	ENST00000613922.2	c.180C>T	p.Pro60Pro	synonymous_variant	2/3	1	NM_002983.3	ENSP00000477908.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30770 AN: 152036 Hom.: 3356 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.206

GnomAD3 exomes AF: 0.226 AC: 56802 AN: 251210 Hom.: 6791 AF XY: 0.227 AC XY: 30850 AN XY: 135760

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.220

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.341

Gnomad SAS exome AF: 0.225

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.216

GnomAD4 exome AF: 0.229 AC: 334876 AN: 1459640 Hom.: 37584 Cov.: 35 AF XY: 0.230 AC XY: 166876 AN XY: 726180

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.226

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.202 AC: 30777 AN: 152156 Hom.: 3360 Cov.: 32 AF XY: 0.200 AC XY: 14890 AN XY: 74382

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.204

Alfa AF: 0.224 Hom.: 2295

Bravo AF: 0.206

Asia WGS AF: 0.310 AC: 1076 AN: 3478

EpiCase AF: 0.236

EpiControl AF: 0.237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.62
DANN	Benign	0.87

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

Other links and lift over

dbSNP: rs1130371; hg19: chr17-34416537;