rs2304970

Positions:

• chr17-4739492-C-A
• chr17-4739492-C-G

Variant summary

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

The NM_001386809.1(CXCL16):​c.-153G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,125,220 control chromosomes in the GnomAD database, including 171,660 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 0.56 (23637 hom., cov: 34)
  • Exomes 𝑓: 0.55 (148023 hom.)
• Consequence: CXCL16 NM_001386809.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL16	NM_001386809.1	c.-153G>T		5_prime_UTR_variant	1/6	ENST00000293778.12
CXCL16	NM_001100812.2	c.-153G>T		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL16	ENST00000293778.12	c.-153G>T		5_prime_UTR_variant	1/6	1	NM_001386809.1	P1
CXCL16	ENST00000574412.6	c.-153G>T		5_prime_UTR_variant	1/5	1		P1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84551 AN: 151946 Hom.: 23612 Cov.: 34

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.590

GnomAD4 exome AF: 0.548 AC: 533334 AN: 973156 Hom.: 148023 Cov.: 13 AF XY: 0.551 AC XY: 273685 AN XY: 496866

Gnomad4 AFR exome AF: 0.557

Gnomad4 AMR exome AF: 0.614

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.578

Gnomad4 SAS exome AF: 0.596

Gnomad4 FIN exome AF: 0.525

Gnomad4 NFE exome AF: 0.537

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.557 AC: 84633 AN: 152064 Hom.: 23637 Cov.: 34 AF XY: 0.558 AC XY: 41507 AN XY: 74330

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.590

Alfa AF: 0.467 Hom.: 1888

Bravo AF: 0.564

Asia WGS AF: 0.616 AC: 2144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.3
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2304970; hg19: chr17-4642787;