rs41409645

Positions:

• chr17-36090134-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002983.3(CCL3):​c.-76C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,388,082 control chromosomes in the GnomAD database, including 6 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 0.0047 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (2 hom.)
• Consequence: CCL3 NM_002983.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00468 (713/152292) while in subpopulation AFR AF= 0.0162 (672/41540). AF 95% confidence interval is 0.0152. There are 4 homozygotes in gnomad4. There are 340 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL3	NM_002983.3	c.-76C>T		5_prime_UTR_premature_start_codon_gain_variant	1/3	ENST00000613922.2	NP_002974.1
CCL3	NM_002983.3	c.-76C>T		5_prime_UTR_variant	1/3	ENST00000613922.2	NP_002974.1
CCL3	NR_168494.1	n.10C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL3	ENST00000613922.2	c.-76C>T		5_prime_UTR_premature_start_codon_gain_variant	1/3	1	NM_002983.3	ENSP00000477908.1
CCL3	ENST00000613922.2	c.-76C>T		5_prime_UTR_variant	1/3	1	NM_002983.3	ENSP00000477908.1

Frequencies

GnomAD3 genomes AF: 0.00468 AC: 712 AN: 152174 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.000456 AC: 563 AN: 1235790 Hom.: 2 Cov.: 18 AF XY: 0.000420 AC XY: 260 AN XY: 619504

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.00122

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000260

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000648

Gnomad4 OTH exome AF: 0.000988

GnomAD4 genome AF: 0.00468 AC: 713 AN: 152292 Hom.: 4 Cov.: 32 AF XY: 0.00457 AC XY: 340 AN XY: 74468

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00225 Hom.: 0

Bravo AF: 0.00497

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.80

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: rs41409645; hg19: chr17-34417480;