rs2282691

Variant names:

• chr17-34361290-T-A
• rs2282691
• NM_002981.2:c.188+495A>T

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+495A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,990 control chromosomes in the GnomAD database, including 27,063 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 0.59 (27063 hom., cov: 32)
• Consequence: CCL1 NM_002981.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL1	NM_002981.2	c.188+495A>T		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+495A>T		intron_variant	Intron 2 of 2	1	NM_002981.2	ENSP00000225842.3

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89871 AN: 151872 Hom.: 27051 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.592 AC: 89912 AN: 151990 Hom.: 27063 Cov.: 32 AF XY: 0.591 AC XY: 43864 AN XY: 74276

African (AFR) AF: 0.519 AC: 21522 AN: 41430

American (AMR) AF: 0.467 AC: 7137 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2347 AN: 3472

East Asian (EAS) AF: 0.608 AC: 3129 AN: 5146

South Asian (SAS) AF: 0.709 AC: 3411 AN: 4812

European-Finnish (FIN) AF: 0.588 AC: 6208 AN: 10556

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.649 AC: 44135 AN: 67972

Other (OTH) AF: 0.605 AC: 1278 AN: 2114

Alfa AF: 0.618 Hom.: 3683

Bravo AF: 0.579

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.34
DANN	Benign	0.45
PhyloP100		-1.0
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: rs2282691; hg19: chr17-32688309;