rs2304973

Positions:

• chr17-4738927-G-A

Variant summary

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

The NM_001386809.1(CXCL16):​c.80-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 1,612,952 control chromosomes in the GnomAD database, including 7,133 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.076 (529 hom., cov: 30)
  • Exomes 𝑓: 0.088 (6604 hom.)
• Consequence: CXCL16 NM_001386809.1 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002511
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCL16	NM_001386809.1	c.80-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000293778.12
CXCL16	NM_001100812.2	c.80-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCL16	ENST00000293778.12	c.80-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001386809.1	P1
CXCL16	ENST00000574412.6	c.80-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		P1
CXCL16	ENST00000573123.1	c.-90C>T		5_prime_UTR_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.0764 AC: 11598 AN: 151800 Hom.: 527 Cov.: 30

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0805

Gnomad OTH AF: 0.0947

GnomAD3 exomes AF: 0.0989 AC: 24768 AN: 250372 Hom.: 1481 AF XY: 0.105 AC XY: 14257 AN XY: 135338

Gnomad AFR exome AF: 0.0350

Gnomad AMR exome AF: 0.0899

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.0781

Gnomad SAS exome AF: 0.191

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0820

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.0881 AC: 128716 AN: 1461034 Hom.: 6604 Cov.: 36 AF XY: 0.0918 AC XY: 66700 AN XY: 726828

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.0912

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.0792

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.0793

Gnomad4 OTH exome AF: 0.0919

GnomAD4 genome AF: 0.0764 AC: 11603 AN: 151918 Hom.: 529 Cov.: 30 AF XY: 0.0794 AC XY: 5893 AN XY: 74252

Gnomad4 AFR AF: 0.0389

Gnomad4 AMR AF: 0.0847

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0848

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0805

Gnomad4 OTH AF: 0.0933

Alfa AF: 0.0862 Hom.: 1091

Bravo AF: 0.0710

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.020		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: rs2304973; hg19: chr17-4642222; COSMIC: COSV52641918; COSMIC: COSV52641918;