Genetic Variant CXCL16:c.-153G>T (chr17-4739492-C-A) – 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.-153G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,125,220 control chromosomes in the GnomAD database, including 171,660 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 0.56 ( 23637 hom., cov: 34)

Exomes 𝑓: 0.55 ( 148023 hom. )

Consequence

CXCL16
NM_001386809.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

Publications

7 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=-0.77).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL16	NM_001386809.1 link	c.-153G>T		5_prime_UTR_variant	Exon 1 of 6	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2 link	c.-153G>T		5_prime_UTR_variant	Exon 1 of 5		NP_001094282.2	Q9H2A7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL16	ENST00000293778.12 link	c.-153G>T		5_prime_UTR_variant	Exon 1 of 6	1	NM_001386809.1	ENSP00000293778.7		Q9H2A7
CXCL16	ENST00000574412.6 link	c.-153G>T		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000459592.2		Q9H2A7

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84551

AN:

151946

Hom.:

23612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.621

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.600

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.520

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.590

GnomAD4 exome

AF:

0.548

AC:

533334

AN:

973156

Hom.:

148023

Cov.:

AF XY:

0.551

AC XY:

273685

AN XY:

496866

show subpopulations

African (AFR)

AF:

0.557

AC:

12754

AN:

22892

American (AMR)

AF:

0.614

AC:

18763

AN:

30536

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

13029

AN:

21318

East Asian (EAS)

AF:

0.578

AC:

19669

AN:

34026

South Asian (SAS)

AF:

0.596

AC:

42094

AN:

70676

European-Finnish (FIN)

AF:

0.525

AC:

18298

AN:

34878

Middle Eastern (MID)

AF:

0.569

AC:

1796

AN:

3156

European-Non Finnish (NFE)

AF:

0.537

AC:

382503

AN:

711896

Other (OTH)

AF:

0.558

AC:

24428

AN:

43778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

12622

25244

37865

50487

63109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9062

18124

27186

36248

45310

<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:

0.557

AC:

84633

AN:

152064

Hom.:

23637

Cov.:

AF XY:

0.558

AC XY:

41507

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.557

AC:

23116

AN:

41512

American (AMR)

AF:

0.621

AC:

9488

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

2145

AN:

3464

East Asian (EAS)

AF:

0.601

AC:

3078

AN:

5120

South Asian (SAS)

AF:

0.590

AC:

2842

AN:

4820

European-Finnish (FIN)

AF:

0.520

AC:

5517

AN:

10600

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.539

AC:

36645

AN:

67944

Other (OTH)

AF:

0.590

AC:

1245

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1955

3910

5866

7821

9776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.467

Hom.:

1888

Bravo

AF:

0.564

Asia WGS

AF:

0.616

AC:

2144

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.3

(source)

DANN

Benign

0.74

PhyloP100

-1.5

PromoterAI

-0.0038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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