dbSNP rs4796195: CCL4L2:c.*57G>A (chr17-36212480-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001291475.2(CCL4L2):c.*57G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,578,468 control chromosomes in the GnomAD database, including 458,970 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 0.71 ( 33451 hom., cov: 37)

Exomes 𝑓: 0.77 ( 425519 hom. )

Consequence

CCL4L2
NM_001291475.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.43

Publications

9 publications found

Variant links:

Genes affected

CCL4L2 (HGNC:24066): (C-C motif chemokine ligand 4 like 2) This gene is one of several cytokine genes that are clustered on the q-arm of chromosome 17. Cytokines are a family of secreted proteins that function in inflammatory and immunoregulatory processes. The protein encoded by this family member is similar to the chemokine (C-C motif) ligand 4 product, which inhibits HIV entry by binding to the cellular receptor CCR5. The copy number of this gene varies among individuals, where most individuals have one to five copies. This gene copy contains a non-consensus splice acceptor site at the 3' terminal exon found in other highly similar gene copies, and it thus uses other alternative splice sites for the 3' terminal exon, resulting in multiple transcript variants. [provided by RefSeq, Apr 2014]

CCL4L2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.12327).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL4L2	NM_001291475.2 link	c.*57G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000617405.5	NP_001278404.1	Q8NHW4-4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCL4L2	ENST00000617405.5 link	c.*57G>A	3_prime_UTR_variant	Exon 3 of 3	1	NM_001291475.2	ENSP00000483330.1	Q8NHW4-4
CCL4L2	ENST00000620250.1 link	c.192-2G>A	splice_acceptor_variant, intron_variant	Intron 2 of 2	1		ENSP00000483609.1	Q8NHW4-1
CCL4L2	ENST00000620576.5 link	c.192-17G>A	intron_variant	Intron 2 of 2	1		ENSP00000479354.1	Q8NHW4-2

Frequencies

GnomAD3 genomes

AF:

0.706

AC:

103414

AN:

146516

Hom.:

33445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.572

Gnomad AMI

AF:

0.820

Gnomad AMR

AF:

0.643

Gnomad ASJ

AF:

0.777

Gnomad EAS

AF:

0.616

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.796

Gnomad OTH

AF:

0.720

GnomAD2 exomes

AF:

0.00505

AC:

633

AN:

125266

AF XY:

0.00456

show subpopulations

Gnomad AFR exome

AF:

0.0237

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.000571

Gnomad EAS exome

AF:

0.00243

Gnomad FIN exome

AF:

0.00633

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.00545

GnomAD4 exome

AF:

0.773

AC:

1106125

AN:

1431838

Hom.:

425519

Cov.:

AF XY:

0.771

AC XY:

549227

AN XY:

712058

show subpopulations

African (AFR)

AF:

0.569

AC:

18758

AN:

32990

American (AMR)

AF:

0.604

AC:

26664

AN:

44122

Ashkenazi Jewish (ASJ)

AF:

0.790

AC:

19636

AN:

24862

East Asian (EAS)

AF:

0.605

AC:

23865

AN:

39438

South Asian (SAS)

AF:

0.682

AC:

57592

AN:

84460

European-Finnish (FIN)

AF:

0.774

AC:

39791

AN:

51394

Middle Eastern (MID)

AF:

0.785

AC:

4210

AN:

5364

European-Non Finnish (NFE)

AF:

0.799

AC:

871078

AN:

1090128

Other (OTH)

AF:

0.754

AC:

44531

AN:

59080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

8697

17394

26091

34788

43485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20202

40404

60606

80808

101010

<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:

0.706

AC:

103476

AN:

146630

Hom.:

33451

Cov.:

AF XY:

0.703

AC XY:

50201

AN XY:

71460

show subpopulations

African (AFR)

AF:

0.572

AC:

23172

AN:

40480

American (AMR)

AF:

0.643

AC:

9400

AN:

14630

Ashkenazi Jewish (ASJ)

AF:

0.777

AC:

2545

AN:

3276

East Asian (EAS)

AF:

0.615

AC:

3107

AN:

5048

South Asian (SAS)

AF:

0.675

AC:

3091

AN:

4580

European-Finnish (FIN)

AF:

0.766

AC:

7464

AN:

9744

Middle Eastern (MID)

AF:

0.794

AC:

224

AN:

282

European-Non Finnish (NFE)

AF:

0.796

AC:

52339

AN:

65742

Other (OTH)

AF:

0.721

AC:

1463

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.562

Heterozygous variant carriers

941

1881

2822

3762

4703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<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:

0.727

Hom.:

2996

ExAC

AF:

0.00479

AC:

317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.85

Eigen

Benign

0.11

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.0055

PhyloP100

3.4

GERP RS

2.9

Mutation Taster

=82/18

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