Genetic Variant CXCL16:c.218+8T>C (chr17-4738774-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001386809.1(CXCL16):c.218+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 1,612,772 control chromosomes in the GnomAD database, including 517,122 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.74 ( 42191 hom., cov: 32)

Exomes 𝑓: 0.80 ( 474931 hom. )

Consequence

CXCL16
NM_001386809.1 splice_region, intron

Scores

Splicing: ADA: 0.0001153

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

Publications

26 publications found

Variant links:

Genes affected

CXCL16 (HGNC:16642): (C-X-C motif chemokine ligand 16) Enables chemokine activity. Involved in several processes, including positive regulation of cell growth; response to interferon-gamma; and response to tumor necrosis factor. Located in extracellular space. Biomarker of COVID-19 and systemic scleroderma. [provided by Alliance of Genome Resources, Apr 2022]

CXCL16 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL16	NM_001386809.1 link	c.218+8T>C		splice_region_variant, intron_variant	Intron 2 of 5	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2 link	c.218+8T>C		splice_region_variant, intron_variant	Intron 2 of 4		NP_001094282.2	Q9H2A7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CXCL16	ENST00000293778.12 link	c.218+8T>C	splice_region_variant, intron_variant	Intron 2 of 5	1	NM_001386809.1	ENSP00000293778.7	Q9H2A7
CXCL16	ENST00000574412.6 link	c.218+8T>C	splice_region_variant, intron_variant	Intron 2 of 4	1		ENSP00000459592.2	Q9H2A7
CXCL16	ENST00000573123.1 link	c.56+8T>C	splice_region_variant, intron_variant	Intron 1 of 2	2		ENSP00000460145.1	I3L333
CXCL16	ENST00000575168.1 link	n.-235T>C	upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.736

AC:

111881

AN:

152034

Hom.:

42148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.562

Gnomad AMI

AF:

0.844

Gnomad AMR

AF:

0.775

Gnomad ASJ

AF:

0.841

Gnomad EAS

AF:

0.710

Gnomad SAS

AF:

0.670

Gnomad FIN

AF:

0.761

Gnomad MID

AF:

0.857

Gnomad NFE

AF:

0.827

Gnomad OTH

AF:

0.766

GnomAD2 exomes

AF:

0.762

AC:

190411

AN:

250032

AF XY:

0.764

show subpopulations

Gnomad AFR exome

AF:

0.551

Gnomad AMR exome

AF:

0.723

Gnomad ASJ exome

AF:

0.849

Gnomad EAS exome

AF:

0.694

Gnomad FIN exome

AF:

0.766

Gnomad NFE exome

AF:

0.823

Gnomad OTH exome

AF:

0.795

GnomAD4 exome

AF:

0.804

AC:

1174427

AN:

1460620

Hom.:

474931

Cov.:

AF XY:

0.802

AC XY:

582889

AN XY:

726584

show subpopulations

African (AFR)

AF:

0.560

AC:

18713

AN:

33434

American (AMR)

AF:

0.728

AC:

32401

AN:

44482

Ashkenazi Jewish (ASJ)

AF:

0.843

AC:

22011

AN:

26098

East Asian (EAS)

AF:

0.708

AC:

28091

AN:

39660

South Asian (SAS)

AF:

0.692

AC:

59624

AN:

86166

European-Finnish (FIN)

AF:

0.764

AC:

40820

AN:

53396

Middle Eastern (MID)

AF:

0.788

AC:

4541

AN:

5760

European-Non Finnish (NFE)

AF:

0.828

AC:

920425

AN:

1111292

Other (OTH)

AF:

0.792

AC:

47801

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

11397

22794

34190

45587

56984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20932

41864

62796

83728

104660

<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:

0.736

AC:

111974

AN:

152152

Hom.:

42191

Cov.:

AF XY:

0.732

AC XY:

54443

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.562

AC:

23331

AN:

41482

American (AMR)

AF:

0.775

AC:

11848

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.841

AC:

2917

AN:

3470

East Asian (EAS)

AF:

0.710

AC:

3676

AN:

5174

South Asian (SAS)

AF:

0.671

AC:

3232

AN:

4820

European-Finnish (FIN)

AF:

0.761

AC:

8060

AN:

10596

Middle Eastern (MID)

AF:

0.856

AC:

250

AN:

292

European-Non Finnish (NFE)

AF:

0.828

AC:

56269

AN:

67996

Other (OTH)

AF:

0.766

AC:

1621

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1423

2846

4268

5691

7114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

840

1680

2520

3360

4200

<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:

0.795

Hom.:

169333

Bravo

AF:

0.730

Asia WGS

AF:

0.714

AC:

2484

AN:

3478

EpiCase

AF:

0.824

EpiControl

AF:

0.827

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.2

(source)

DANN

Benign

0.74

PhyloP100

1.3

PromoterAI

-0.0068

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0

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