rs3138031

Variant names:

• chr17-34361487-A-C
• rs3138031
• NM_002981.2:c.188+298T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002981.2(CCL1):​c.188+298T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,246 control chromosomes in the GnomAD database, including 1,287 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 0.11 (1287 hom., cov: 33)
• Consequence: CCL1 NM_002981.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486
• Publications: 6 publications found

Genes affected

CCL1 (HGNC:10609): (C-C motif chemokine ligand 1) This antimicrobial gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CC subfamily, is secreted by activated T cells and displays chemotactic activity for monocytes but not for neutrophils. It binds to the chemokine (C-C motif) receptor 8. [provided by RefSeq, Sep 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL1	NM_002981.2	c.188+298T>G		intron_variant	Intron 2 of 2	ENST00000225842.4	NP_002972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL1	ENST00000225842.4	c.188+298T>G		intron_variant	Intron 2 of 2	1	NM_002981.2	ENSP00000225842.3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17518 AN: 152128 Hom.: 1288 Cov.: 33

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17507 AN: 152246 Hom.: 1287 Cov.: 33 AF XY: 0.114 AC XY: 8485 AN XY: 74442

African (AFR) AF: 0.0315 AC: 1309 AN: 41550

American (AMR) AF: 0.133 AC: 2028 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 647 AN: 3468

East Asian (EAS) AF: 0.0305 AC: 158 AN: 5176

South Asian (SAS) AF: 0.109 AC: 527 AN: 4830

European-Finnish (FIN) AF: 0.130 AC: 1377 AN: 10602

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10988 AN: 68006

Other (OTH) AF: 0.134 AC: 282 AN: 2104

Alfa AF: 0.139 Hom.: 2614

Bravo AF: 0.112

Asia WGS AF: 0.0750 AC: 261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.76
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs3138031; hg19: chr17-32688506;