Variant 17-4735268-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001386809.1(CXCL16):c.542C>T(p.Ala181Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,613,650 control chromosomes in the GnomAD database, including 158,490 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.42 ( 13611 hom., cov: 32)

Exomes 𝑓: 0.44 ( 144879 hom. )

Consequence

CXCL16
NM_001386809.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.655

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:

CXCL16 (HGNC:):

CXCL16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.6505287E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL16	NM_001386809.1 linkuse as main transcript	c.542C>T	p.Ala181Val	missense_variant	4/6	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2 linkuse as main transcript	c.542C>T	p.Ala181Val	missense_variant	4/5		NP_001094282.2	Q9H2A7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CXCL16	ENST00000293778.12 linkuse as main transcript	c.542C>T	p.Ala181Val	missense_variant	4/6	1	NM_001386809.1	ENSP00000293778.7	Q9H2A7
CXCL16	ENST00000574412.6 linkuse as main transcript	c.542C>T	p.Ala181Val	missense_variant	4/5	1		ENSP00000459592.2	Q9H2A7
CXCL16	ENST00000576153.5 linkuse as main transcript	c.125C>T	p.Ala42Val	missense_variant	2/4	2		ENSP00000501470.1	A0A6I8PIU7
CXCL16	ENST00000575168.1 linkuse as main transcript	n.373C>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

63111

AN:

151936

Hom.:

13597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.592

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.442

GnomAD3 exomes

AF:

0.468

AC:

117332

AN:

250682

Hom.:

28054

AF XY:

0.470

AC XY:

63699

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.549

Gnomad ASJ exome

AF:

0.466

Gnomad EAS exome

AF:

0.581

Gnomad SAS exome

AF:

0.555

Gnomad FIN exome

AF:

0.453

Gnomad NFE exome

AF:

0.428

Gnomad OTH exome

AF:

0.465

GnomAD4 exome

AF:

0.442

AC:

645763

AN:

1461596

Hom.:

144879

Cov.:

AF XY:

0.445

AC XY:

323886

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.303

Gnomad4 AMR exome

AF:

0.546

Gnomad4 ASJ exome

AF:

0.460

Gnomad4 EAS exome

AF:

0.576

Gnomad4 SAS exome

AF:

0.552

Gnomad4 FIN exome

AF:

0.450

Gnomad4 NFE exome

AF:

0.428

Gnomad4 OTH exome

AF:

0.440

GnomAD4 genome

AF:

0.415

AC:

63173

AN:

152054

Hom.:

13611

Cov.:

AF XY:

0.422

AC XY:

31367

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.305

Gnomad4 AMR

AF:

0.510

Gnomad4 ASJ

AF:

0.455

Gnomad4 EAS

AF:

0.593

Gnomad4 SAS

AF:

0.540

Gnomad4 FIN

AF:

0.456

Gnomad4 NFE

AF:

0.431

Gnomad4 OTH

AF:

0.441

Alfa

AF:

0.436

Hom.:

32072

Bravo

AF:

0.414

TwinsUK

AF:

0.430

AC:

1595

ALSPAC

AF:

0.442

AC:

1705

ESP6500AA

AF:

0.313

AC:

1377

ESP6500EA

AF:

0.437

AC:

3756

ExAC

AF:

0.460

AC:

55866

Asia WGS

AF:

0.567

AC:

1973

AN:

3478

EpiCase

AF:

0.426

EpiControl

AF:

0.439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.49

DANN

Benign

0.51

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.043

MetaRNN

Benign

0.000047

T;T

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.018

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Vest4

0.016

MPC

0.17

ClinPred

0.0083

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over