Genetic Variant NM_001291475.2:c.*57G>A (chr17-36212480-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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	ENST00000620576.4 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

GnomAD3 exomes

AF:

0.00505

AC:

633

AN:

125266

Hom.:

234

AF XY:

0.00456

AC XY:

299

AN XY:

65588

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 SAS exome

AF:

0.00598

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

Gnomad4 AFR exome

AF:

0.569

Gnomad4 AMR exome

AF:

0.604

Gnomad4 ASJ exome

AF:

0.790

Gnomad4 EAS exome

AF:

0.605

Gnomad4 SAS exome

AF:

0.682

Gnomad4 FIN exome

AF:

0.774

Gnomad4 NFE exome

AF:

0.799

Gnomad4 OTH exome

AF:

0.754

GnomAD4 genome

AF:

0.706

AC:

103476

AN:

146630

Hom.:

33451

Cov.:

AF XY:

0.703

AC XY:

50201

AN XY:

71460

show subpopulations

Gnomad4 AFR

AF:

0.572

Gnomad4 AMR

AF:

0.643

Gnomad4 ASJ

AF:

0.777

Gnomad4 EAS

AF:

0.615

Gnomad4 SAS

AF:

0.675

Gnomad4 FIN

AF:

0.766

Gnomad4 NFE

AF:

0.796

Gnomad4 OTH

AF:

0.721

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

DANN

Benign

0.85

Eigen

Benign

0.11

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.0055

GERP RS

2.9

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over