17-4735235-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 25 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL16	ENST00000293778.12	c.575C>T	p.Pro192Leu	missense_variant	4/6	1	NM_001386809.1	P1
CXCL16	ENST00000574412.6	c.575C>T	p.Pro192Leu	missense_variant	4/5	1		P1
CXCL16	ENST00000576153.5	c.158C>T	p.Pro53Leu	missense_variant	2/4	2
CXCL16	ENST00000575168.1	n.406C>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1559 AN: 152134 Hom.: 25 Cov.: 33

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.: 9 AF XY: 0.00218 AC XY: 296 AN XY: 135678

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.: 25 Cov.: 59 AF XY: 0.00131 AC XY: 956 AN XY: 727186

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.: 26 Cov.: 33 AF XY: 0.00986 AC XY: 734 AN XY: 74456

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.: 7

Bravo AF: 0.0126

ESP6500AA AF: 0.0320 AC: 141

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00329 AC: 399

EpiCase AF: 0.000491

EpiControl AF: 0.000475

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.71	T
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	N
MetaRNN	Benign	0.0021	T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.22	T
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	T
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

Other links and lift over

dbSNP: rs61463072; hg19: chr17-4638530;