chr17-4735189-T-C

Position:

• chr17-4735189-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001386809.1(CXCL16):​c.621A>G​(p.Pro207Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,613,558 control chromosomes in the GnomAD database, including 250,546 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 0.52 (20911 hom., cov: 32)
  • Exomes 𝑓: 0.56 (229635 hom.)
• Consequence: CXCL16 NM_001386809.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.78

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-5.78 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL16	NM_001386809.1	c.621A>G	p.Pro207Pro	synonymous_variant	4/6	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2	c.621A>G	p.Pro207Pro	synonymous_variant	4/5		NP_001094282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL16	ENST00000293778.12	c.621A>G	p.Pro207Pro	synonymous_variant	4/6	1	NM_001386809.1	ENSP00000293778.7
CXCL16	ENST00000574412.6	c.621A>G	p.Pro207Pro	synonymous_variant	4/5	1		ENSP00000459592.2
CXCL16	ENST00000576153.5	c.204A>G	p.Pro68Pro	synonymous_variant	2/4	2		ENSP00000501470.1
CXCL16	ENST00000575168.1	n.452A>G		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78574 AN: 151996 Hom.: 20888 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.563

GnomAD3 exomes AF: 0.564 AC: 141351 AN: 250504 Hom.: 40143 AF XY: 0.567 AC XY: 76786 AN XY: 135396

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.609

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.585

Gnomad SAS exome AF: 0.621

Gnomad FIN exome AF: 0.540

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.579

GnomAD4 exome AF: 0.559 AC: 816989 AN: 1461444 Hom.: 229635 Cov.: 55 AF XY: 0.562 AC XY: 408363 AN XY: 726986

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.610

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.578

Gnomad4 SAS exome AF: 0.620

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.562

GnomAD4 genome AF: 0.517 AC: 78653 AN: 152114 Hom.: 20911 Cov.: 32 AF XY: 0.520 AC XY: 38646 AN XY: 74352

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.563

Alfa AF: 0.549 Hom.: 17992

Bravo AF: 0.517

Asia WGS AF: 0.621 AC: 2160 AN: 3478

EpiCase AF: 0.557

EpiControl AF: 0.567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.059
DANN	Benign	0.41

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: rs1876444; hg19: chr17-4638484; COSMIC: COSV53411281; COSMIC: COSV53411281;