Genetic Variant CXCL16:c.719-63A>C (chr17-4734715-T-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.719-63A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,365,264 control chromosomes in the GnomAD database, including 323,322 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 0.66 ( 34000 hom., cov: 31)

Exomes 𝑓: 0.69 ( 289322 hom. )

Consequence

CXCL16
NM_001386809.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.822

Publications

30 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386809.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL16	NM_001386809.1	MANE Select	c.719-63A>C		intron	N/A	NP_001373738.1	Q9H2A7
	CXCL16	NM_001100812.2		c.719-63A>C		intron	N/A	NP_001094282.2	Q9H2A7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CXCL16	ENST00000293778.12	TSL:1 MANE Select	c.719-63A>C	intron	N/A	ENSP00000293778.7	Q9H2A7
CXCL16	ENST00000574412.6	TSL:1	c.719-63A>C	intron	N/A	ENSP00000459592.2	Q9H2A7
CXCL16	ENST00000886021.1		c.719-63A>C	intron	N/A	ENSP00000556080.1

Frequencies

GnomAD3 genomes

AF:

0.664

AC:

100915

AN:

151894

Hom.:

33985

Cov.:

show subpopulations

Gnomad AFR

AF:

0.576

Gnomad AMI

AF:

0.589

Gnomad AMR

AF:

0.743

Gnomad ASJ

AF:

0.673

Gnomad EAS

AF:

0.886

Gnomad SAS

AF:

0.882

Gnomad FIN

AF:

0.748

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.656

Gnomad OTH

AF:

0.672

GnomAD4 exome

AF:

0.687

AC:

833205

AN:

1213252

Hom.:

289322

AF XY:

0.693

AC XY:

426679

AN XY:

616090

show subpopulations

African (AFR)

AF:

0.574

AC:

16432

AN:

28650

American (AMR)

AF:

0.829

AC:

36654

AN:

44216

Ashkenazi Jewish (ASJ)

AF:

0.677

AC:

16590

AN:

24514

East Asian (EAS)

AF:

0.869

AC:

33393

AN:

38440

South Asian (SAS)

AF:

0.872

AC:

70609

AN:

80986

European-Finnish (FIN)

AF:

0.736

AC:

38995

AN:

52988

Middle Eastern (MID)

AF:

0.706

AC:

3728

AN:

5284

European-Non Finnish (NFE)

AF:

0.656

AC:

581372

AN:

885938

Other (OTH)

AF:

0.678

AC:

35432

AN:

52236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

12504

25007

37511

50014

62518

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13866

27732

41598

55464

69330

<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:

0.664

AC:

100970

AN:

152012

Hom.:

34000

Cov.:

AF XY:

0.676

AC XY:

50239

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.575

AC:

23836

AN:

41430

American (AMR)

AF:

0.743

AC:

11352

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.673

AC:

2335

AN:

3472

East Asian (EAS)

AF:

0.887

AC:

4584

AN:

5170

South Asian (SAS)

AF:

0.882

AC:

4262

AN:

4832

European-Finnish (FIN)

AF:

0.748

AC:

7904

AN:

10564

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.656

AC:

44565

AN:

67956

Other (OTH)

AF:

0.671

AC:

1418

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1722

3444

5165

6887

8609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.666

Hom.:

67761

Bravo

AF:

0.657

Asia WGS

AF:

0.850

AC:

2955

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.7

(source)

DANN

Benign

0.71

PhyloP100

-0.82

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over