rs34171309

Positions:

• chr17-36088717-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002983.3(CCL3):​c.234G>T​(p.Glu78Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,613,780 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.024 (160 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (151 hom.)
• Consequence: CCL3 NM_002983.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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 (MetaRNN=0.0017627776).
• BP6: Variant 17-36088717-C-A is Benign according to our data. Variant chr17-36088717-C-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL3	NM_002983.3	c.234G>T	p.Glu78Asp	missense_variant	3/3	ENST00000613922.2
CCL3	NR_168494.1	n.1007G>T		non_coding_transcript_exon_variant	2/2
CCL3	NR_168495.1	n.217G>T		non_coding_transcript_exon_variant	3/3
CCL3	NR_168496.1	n.180G>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL3	ENST00000613922.2	c.234G>T	p.Glu78Asp	missense_variant	3/3	1	NM_002983.3	P1
CCL3-AS1	ENST00000620056.4	n.390-829C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3699 AN: 152078 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.0272

GnomAD3 exomes AF: 0.00808 AC: 2030 AN: 251206 Hom.: 75 AF XY: 0.00651 AC XY: 884 AN XY: 135766

Gnomad AFR exome AF: 0.0826

Gnomad AMR exome AF: 0.00980

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00225

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.00403 AC: 5886 AN: 1461584 Hom.: 151 Cov.: 31 AF XY: 0.00374 AC XY: 2717 AN XY: 727094

Gnomad4 AFR exome AF: 0.0805

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00176

Gnomad4 OTH exome AF: 0.00964

GnomAD4 genome AF: 0.0244 AC: 3715 AN: 152196 Hom.: 160 Cov.: 32 AF XY: 0.0246 AC XY: 1831 AN XY: 74404

Gnomad4 AFR AF: 0.0785

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00196

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0116 Hom.: 26

Bravo AF: 0.0282

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.0865 AC: 381

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.00941 AC: 1142

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.00234

EpiControl AF: 0.00279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.1
DANN	Benign	0.79
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.058	N
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.75	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.12		Loss of catalytic residue at W80 (P = 0.0511);
MVP		0.40
ClinPred		0.0035	T
GERP RS		1.3
Varity_R		0.35
gMVP		0.30

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: rs34171309; hg19: chr17-34416063;