17-34361693-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002981.2(CCL1):c.188+92A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.976 in 880,384 control chromosomes in the GnomAD database, including 421,800 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 0.91 (64669 hom., cov: 32)
  • Exomes 𝑓: 0.99 (357131 hom.)
• Consequence: CCL1 NM_002981.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL1	NM_002981.2	c.188+92A>G		intron_variant		ENST00000225842.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL1	ENST00000225842.4	c.188+92A>G		intron_variant		1	NM_002981.2	P1

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138711 AN: 152126 Hom.: 64632 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.940

GnomAD4 exome AF: 0.989 AC: 720203 AN: 728140 Hom.: 357131 AF XY: 0.991 AC XY: 374205 AN XY: 377670

Gnomad4 AFR exome AF: 0.692

Gnomad4 AMR exome AF: 0.982

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.979

GnomAD4 genome AF: 0.912 AC: 138800 AN: 152244 Hom.: 64669 Cov.: 32 AF XY: 0.916 AC XY: 68163 AN XY: 74444

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.962

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.941

Alfa AF: 0.981 Hom.: 63139

Bravo AF: 0.901

Asia WGS AF: 0.976 AC: 3393 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.0
Dann	Benign	0.53

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: rs159271; hg19: chr17-32688712;