rs5029410

Positions:

• chr17-36088805-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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 -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/exons	MANE	UniProt
CCL3	NM_002983.3	c.189-43T>G		intron_variant		ENST00000613922.2
CCL3	NR_168494.1	n.962-43T>G		intron_variant, non_coding_transcript_variant
CCL3	NR_168495.1	n.172-43T>G		intron_variant, non_coding_transcript_variant
CCL3	NR_168496.1	n.135-43T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL3	ENST00000613922.2	c.189-43T>G		intron_variant		1	NM_002983.3	P1
CCL3-AS1	ENST00000620056.4	n.390-741A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3610 AN: 152178 Hom.: 129 Cov.: 32

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

GnomAD3 exomes AF: 0.00750 AC: 1879 AN: 250692 Hom.: 51 AF XY: 0.00590 AC XY: 800 AN XY: 135544

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 SAS exome AF: 0.00464

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.: 29 AF XY: 0.00302 AC XY: 2193 AN XY: 725562

Gnomad4 AFR exome AF: 0.0853

Gnomad4 AMR exome AF: 0.00837

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00443

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.000523

Gnomad4 OTH exome AF: 0.00626

GnomAD4 genome AF: 0.0238 AC: 3623 AN: 152296 Hom.: 131 Cov.: 32 AF XY: 0.0233 AC XY: 1736 AN XY: 74488

Gnomad4 AFR AF: 0.0805

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000764

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0101 Hom.: 11

Bravo AF: 0.0275

Asia WGS AF: 0.00549 AC: 19 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
DANN	Benign	0.75

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: rs5029410; hg19: chr17-34416151;