Variant chr17-36212546-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001291468.2(CCL4L2):c.241G>A(p.Val81Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000794 in 1,581,370 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 3 hom., cov: 36)

Exomes 𝑓: 0.00084 ( 141 hom. )

Consequence

CCL4L2
NM_001291468.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030037135).

BP6

Variant 17-36212546-G-A is Benign according to our data. Variant chr17-36212546-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2352114.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL4L2	NM_001291475.2 link	c.*123G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000617405.5	NP_001278404.1	Q8NHW4-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCL4L2	ENST00000620250.1 link	c.256G>A	p.Val86Met	missense_variant	Exon 3 of 3	1		ENSP00000483609.1	Q8NHW4-1
CCL4L2	ENST00000620576.4 link	c.241G>A	p.Val81Met	missense_variant	Exon 3 of 3	1		ENSP00000479354.1	Q8NHW4-2
CCL4L2	ENST00000617405.5 link	c.*123G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_001291475.2	ENSP00000483330.1	Q8NHW4-4

Frequencies

GnomAD3 genomes

AF:

0.000343

AC:

AN:

148636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000674

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000694

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000331

AC:

AN:

120752

Hom.:

AF XY:

0.0000477

AC XY:

AN XY:

62940

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000523

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000841

AC:

1205

AN:

1432734

Hom.:

141

Cov.:

AF XY:

0.000787

AC XY:

561

AN XY:

712482

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000904

Gnomad4 ASJ exome

AF:

0.0000402

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000195

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.00139

GnomAD4 genome

AF:

0.000343

AC:

AN:

148636

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

AN XY:

72488

show subpopulations

Gnomad4 AFR

AF:

0.0000968

Gnomad4 AMR

AF:

0.0000674

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000694

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000498

Hom.:

ESP6500AA

AF:

0.000543

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000970

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 12, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.40

DANN

Benign

0.88

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0046

M_CAP

Benign

0.0032

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-0.92

Sift4G

Benign

0.39

T;T

Vest4

0.10

MVP

0.014

ClinPred

0.023

GERP RS

-2.4

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over