Genetic Variant NM_002981.2:c.188+92A>G (chr17-34361693-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.163

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCL1	NM_002981.2 link	c.188+92A>G		intron_variant	Intron 2 of 2	ENST00000225842.4	NP_002972.1	P22362

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL1	ENST00000225842.4 link	c.188+92A>G		intron_variant	Intron 2 of 2	1	NM_002981.2	ENSP00000225842.3		P22362

Frequencies

GnomAD3 genomes

AF:

0.912

AC:

138711

AN:

152126

Hom.:

64632

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.692

AC:

13512

AN:

19532

American (AMR)

AF:

0.982

AC:

37393

AN:

38068

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

18038

AN:

18058

East Asian (EAS)

AF:

0.999

AC:

35417

AN:

35446

South Asian (SAS)

AF:

0.999

AC:

56874

AN:

56922

European-Finnish (FIN)

AF:

1.00

AC:

47141

AN:

47142

Middle Eastern (MID)

AF:

0.985

AC:

2841

AN:

2884

European-Non Finnish (NFE)

AF:

0.999

AC:

475836

AN:

476214

Other (OTH)

AF:

0.979

AC:

33151

AN:

33874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

299

599

898

1198

1497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6624

13248

19872

26496

33120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.912

AC:

138800

AN:

152244

Hom.:

64669

Cov.:

AF XY:

0.916

AC XY:

68163

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.695

AC:

28856

AN:

41496

American (AMR)

AF:

0.962

AC:

14724

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.999

AC:

3469

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5163

AN:

5170

South Asian (SAS)

AF:

0.999

AC:

4827

AN:

4830

European-Finnish (FIN)

AF:

1.00

AC:

10618

AN:

10618

Middle Eastern (MID)

AF:

0.976

AC:

287

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67959

AN:

68040

Other (OTH)

AF:

0.941

AC:

1987

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

481

963

1444

1926

2407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.968

Hom.:

83207

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

(source)

DANN

Benign

0.53

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over