rs35511254

Positions:

• chr17-36089946-G-A
• chr17-36089946-G-T

Variant summary

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

The NM_002983.3(CCL3):​c.73+40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 1,572,536 control chromosomes in the GnomAD database, including 314 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 (164 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (150 hom.)
• Consequence: CCL3 NM_002983.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL3	NM_002983.3	c.73+40C>T		intron_variant		ENST00000613922.2
CCL3	NR_168494.1	n.198C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL3	ENST00000613922.2	c.73+40C>T		intron_variant		1	NM_002983.3	P1
CCL3	ENST00000614051.1	n.224C>T		non_coding_transcript_exon_variant	1/2	1
CCL3	ENST00000613928.1	n.189C>T		non_coding_transcript_exon_variant	1/2	5
CCL3-AS1	ENST00000616926.1	n.927G>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3708 AN: 152156 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0785

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.0273

GnomAD3 exomes AF: 0.00806 AC: 2012 AN: 249508 Hom.: 73 AF XY: 0.00649 AC XY: 875 AN XY: 134804

Gnomad AFR exome AF: 0.0831

Gnomad AMR exome AF: 0.00984

Gnomad ASJ exome AF: 0.00269

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00222

Gnomad OTH exome AF: 0.0102

GnomAD4 exome AF: 0.00406 AC: 5762 AN: 1420262 Hom.: 150 Cov.: 27 AF XY: 0.00374 AC XY: 2653 AN XY: 708842

Gnomad4 AFR exome AF: 0.0805

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00190

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000176

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00178

Gnomad4 OTH exome AF: 0.00968

GnomAD4 genome AF: 0.0245 AC: 3724 AN: 152274 Hom.: 164 Cov.: 32 AF XY: 0.0247 AC XY: 1843 AN XY: 74474

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00196

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.00861 Hom.: 6

Bravo AF: 0.0282

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.5
DANN	Benign	0.79

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: rs35511254; hg19: chr17-34417292;