Genetic Variant NM_001291468.2:c.241G>A (chr17-36212546-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 12/15 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

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2352114.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291468.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CCL4L2	NM_001291468.2	MANE Select	c.241G>A	p.Val81Met	missense	Exon 3 of 3	NP_001278397.1
CCL4L2	NM_001291471.2		c.*113G>A		3_prime_UTR	Exon 3 of 3	NP_001278400.1
CCL4L2	NM_001291475.2		c.*123G>A		3_prime_UTR	Exon 3 of 3	NP_001278404.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCL4L2	ENST00000620576.5	TSL:1 MANE Select	c.241G>A	p.Val81Met	missense	Exon 3 of 3	ENSP00000479354.1	Q8NHW4-2
CCL4L2	ENST00000620250.1	TSL:1	c.256G>A	p.Val86Met	missense	Exon 3 of 3	ENSP00000483609.1	Q8NHW4-1
CCL4L2	ENST00000620055.4	TSL:1	c.126G>A	p.Thr42Thr	synonymous	Exon 2 of 2	ENSP00000481323.1	Q8NHW4-7

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

GnomAD2 exomes

AF:

0.0000331

AC:

AN:

120752

AF XY:

0.0000477

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 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

African (AFR)

AF:

0.000120

AC:

AN:

33428

American (AMR)

AF:

0.0000904

AC:

AN:

44260

Ashkenazi Jewish (ASJ)

AF:

0.0000402

AC:

AN:

24870

East Asian (EAS)

AF:

0.00

AC:

AN:

39482

South Asian (SAS)

AF:

0.00

AC:

AN:

84482

European-Finnish (FIN)

AF:

0.0000195

AC:

AN:

51410

Middle Eastern (MID)

AF:

0.000559

AC:

AN:

5370

European-Non Finnish (NFE)

AF:

0.00102

AC:

1110

AN:

1090298

Other (OTH)

AF:

0.00139

AC:

AN:

59134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

103

154

206

257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.000343

AC:

AN:

148636

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

AN XY:

72488

show subpopulations

African (AFR)

AF:

0.0000968

AC:

AN:

41314

American (AMR)

AF:

0.0000674

AC:

AN:

14834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3300

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4632

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

298

European-Non Finnish (NFE)

AF:

0.000694

AC:

AN:

66284

Other (OTH)

AF:

0.00

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000498

Hom.:

ESP6500AA

AF:

0.000543

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000970

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.40

(source)

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

MetaSVM

Benign

-0.92

PhyloP100

-1.1

Sift4G

Benign

0.39

Vest4

0.10

MVP

0.014

ClinPred

0.023

GERP RS

-2.4

Mutation Taster

=98/2

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over