Variant 17-4735235-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001386809.1(CXCL16):c.575C>T(p.Pro192Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,614,044 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 26 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 25 hom. )

Consequence

CXCL16
NM_001386809.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.05

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020643175).

BP6

Variant 17-4735235-G-A is Benign according to our data. Variant chr17-4735235-G-A is described in ClinVar as [Benign]. Clinvar id is 777096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1568/152252) while in subpopulation AFR AF= 0.0333 (1382/41548). AF 95% confidence interval is 0.0318. There are 26 homozygotes in gnomad4. There are 734 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL16	NM_001386809.1 link	c.575C>T	p.Pro192Leu	missense_variant	4/6	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2 link	c.575C>T	p.Pro192Leu	missense_variant	4/5		NP_001094282.2	Q9H2A7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CXCL16	ENST00000293778.12 link	c.575C>T	p.Pro192Leu	missense_variant	4/6	1	NM_001386809.1	ENSP00000293778.7	Q9H2A7
CXCL16	ENST00000574412.6 link	c.575C>T	p.Pro192Leu	missense_variant	4/5	1		ENSP00000459592.2	Q9H2A7
CXCL16	ENST00000576153.5 link	c.158C>T	p.Pro53Leu	missense_variant	2/4	2		ENSP00000501470.1	A0A6I8PIU7
CXCL16	ENST00000575168.1 link	n.406C>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1559

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00883

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.00768

GnomAD3 exomes

AF:

0.00295

AC:

741

AN:

250914

Hom.:

AF XY:

0.00218

AC XY:

296

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.0344

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000450

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00146

AC:

2140

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

956

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0352

Gnomad4 AMR exome

AF:

0.00401

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000470

Gnomad4 OTH exome

AF:

0.00368

GnomAD4 genome

AF:

0.0103

AC:

1568

AN:

152252

Hom.:

Cov.:

AF XY:

0.00986

AC XY:

734

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0333

Gnomad4 AMR

AF:

0.00882

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00760

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.0126

ESP6500AA

AF:

0.0320

AC:

141

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00329

AC:

399

EpiCase

AF:

0.000491

EpiControl

AF:

0.000475

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0090

DANN

Benign

0.49

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.018

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.22

PROVEAN

Benign

3.5

N;.

REVEL

Benign

0.0070

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Vest4

0.13

MVP

0.17

MPC

0.18

ClinPred

0.0016

GERP RS

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.042

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over