Variant chr17-34361803-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_002981.2(CCL1):c.170G>T(p.Cys57Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CCL1
NM_002981.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03

Variant links:

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]

CCL1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.992

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL1	NM_002981.2 link	c.170G>T	p.Cys57Phe	missense_variant	2/3	ENST00000225842.4	NP_002972.1	P22362

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL1	ENST00000225842.4 link	c.170G>T	p.Cys57Phe	missense_variant	2/3	1	NM_002981.2	ENSP00000225842.3		P22362

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725770

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2024

The c.170G>T (p.C57F) alteration is located in exon 2 (coding exon 2) of the CCL1 gene. This alteration results from a G to T substitution at nucleotide position 170, causing the cysteine (C) at amino acid position 57 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.33

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.40

M_CAP

Uncertain

0.28

MetaRNN

Pathogenic

0.99

MetaSVM

Uncertain

0.56

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-11

REVEL

Uncertain

0.61

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.86

MutPred

0.98

Gain of MoRF binding (P = 0.2589);

MVP

0.91

MPC

0.32

ClinPred

1.0

GERP RS

4.4

Varity_R

0.94

gMVP

0.74

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over