rs1130371

Variant names:

• chr17-36089191-G-A
• rs1130371
• NM_002983.3:c.180C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCL3	NM_002983.3	c.180C>T	p.Pro60Pro	synonymous_variant	Exon 2 of 3	ENST00000613922.2	NP_002974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL3	ENST00000613922.2	c.180C>T	p.Pro60Pro	synonymous_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.226 AC: 56802 AN: 251210 AF XY: 0.227

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 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

African (AFR) AF: 0.128 AC: 4272 AN: 33446

American (AMR) AF: 0.210 AC: 9396 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 4976 AN: 26128

East Asian (EAS) AF: 0.323 AC: 12785 AN: 39632

South Asian (SAS) AF: 0.226 AC: 19463 AN: 86174

European-Finnish (FIN) AF: 0.165 AC: 8798 AN: 53420

Middle Eastern (MID) AF: 0.196 AC: 1130 AN: 5754

European-Non Finnish (NFE) AF: 0.235 AC: 260629 AN: 1110094

Other (OTH) AF: 0.223 AC: 13427 AN: 60306

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

African (AFR) AF: 0.134 AC: 5583 AN: 41538

American (AMR) AF: 0.199 AC: 3047 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 596 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1776 AN: 5152

South Asian (SAS) AF: 0.236 AC: 1139 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1648 AN: 10592

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16216 AN: 67988

Other (OTH) AF: 0.204 AC: 428 AN: 2100

Alfa AF: 0.224 Hom.: 2575

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
PhyloP100		-8.3
Mutation Taster		=86/14	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1130371; hg19: chr17-34416537;