17-36090134-G-C

Variant names:

• chr17-36090134-G-C
• rs41409645
• ENST00000614051.1:n.36C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000614051.1(CCL3):​n.36C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000162 in 1,235,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CCL3 ENST00000614051.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL3	NM_002983.3	c.-76C>G		5_prime_UTR_variant	Exon 1 of 3	ENST00000613922.2	NP_002974.1
CCL3	NR_168494.1	n.10C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL3	ENST00000614051.1	n.36C>G		non_coding_transcript_exon_variant	Exon 1 of 2	1
CCL3	ENST00000613922.2	c.-76C>G		5_prime_UTR_variant	Exon 1 of 3	1	NM_002983.3	ENSP00000477908.1
CCL3	ENST00000613928.1	n.1C>G		non_coding_transcript_exon_variant	Exon 1 of 2	5
CCL3-AS1	ENST00000616926.1	n.1115G>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000162 AC: 2 AN: 1235798 Hom.: 0 Cov.: 18 AF XY: 0.00000161 AC XY: 1 AN XY: 619510

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28634

American (AMR) AF: 0.00 AC: 0 AN: 37014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24228

East Asian (EAS) AF: 0.0000553 AC: 2 AN: 36138

South Asian (SAS) AF: 0.00 AC: 0 AN: 76868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3876

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 925726

Other (OTH) AF: 0.00 AC: 0 AN: 52652

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.029673), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.7
DANN	Benign	0.75
PhyloP100		0.45
PromoterAI		-0.077	Neutral

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: rs41409645; hg19: chr17-34417480;