rs1051009

Positions:

• chr17-4734591-G-A
• chr17-4734591-G-C
• chr17-4734591-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386809.1(CXCL16):​c.*15C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,594,374 control chromosomes in the GnomAD database, including 95,233 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 0.28 (7356 hom., cov: 32)
  • Exomes 𝑓: 0.34 (87877 hom.)
• Consequence: CXCL16 NM_001386809.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL16	NM_001386809.1	c.*15C>T		3_prime_UTR_variant	5/6	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2	c.*15C>T		3_prime_UTR_variant	5/5		NP_001094282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL16	ENST00000293778	c.*15C>T		3_prime_UTR_variant	5/6	1	NM_001386809.1	ENSP00000293778.7
CXCL16	ENST00000574412	c.*15C>T		3_prime_UTR_variant	5/5	1		ENSP00000459592.2
CXCL16	ENST00000576153	c.*15C>T		3_prime_UTR_variant	3/4	2		ENSP00000501470.1
CXCL16	ENST00000575168.1	n.611C>T		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42498 AN: 152010 Hom.: 7353 Cov.: 32

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.297

GnomAD3 exomes AF: 0.352 AC: 88372 AN: 251412 Hom.: 16721 AF XY: 0.351 AC XY: 47711 AN XY: 135884

Gnomad AFR exome AF: 0.0630

Gnomad AMR exome AF: 0.448

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.503

Gnomad SAS exome AF: 0.361

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.343

GnomAD4 exome AF: 0.343 AC: 494138 AN: 1442246 Hom.: 87877 Cov.: 28 AF XY: 0.344 AC XY: 247018 AN XY: 718708

Gnomad4 AFR exome AF: 0.0532

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.496

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.279 AC: 42506 AN: 152128 Hom.: 7356 Cov.: 32 AF XY: 0.285 AC XY: 21180 AN XY: 74352

Gnomad4 AFR AF: 0.0679

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.298

Alfa AF: 0.330 Hom.: 9852

Bravo AF: 0.274

Asia WGS AF: 0.428 AC: 1489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1051009; hg19: chr17-4637886; COSMIC: COSV53411277; COSMIC: COSV53411277;