rs2304973

Variant names:

• chr17-4738927-G-A
• rs2304973
• NM_001386809.1:c.80-7C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386809.1(CXCL16):​c.80-7C>T variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.00002511
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386809.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL16	NM_001386809.1	MANE Select	c.80-7C>T		splice_region intron	N/A	NP_001373738.1
	CXCL16	NM_001100812.2		c.80-7C>T		splice_region intron	N/A	NP_001094282.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL16	ENST00000293778.12	TSL:1 MANE Select	c.80-7C>T		splice_region intron	N/A	ENSP00000293778.7
	CXCL16	ENST00000574412.6	TSL:1	c.80-7C>T		splice_region intron	N/A	ENSP00000459592.2
	CXCL16	ENST00000573123.1	TSL:2	c.-90C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000460145.1

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

GnomAD2 exomes AF: 0.0989 AC: 24768 AN: 250372 AF XY: 0.105

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 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

African (AFR) AF: 0.0359 AC: 1201 AN: 33472

American (AMR) AF: 0.0912 AC: 4075 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 4090 AN: 26066

East Asian (EAS) AF: 0.0792 AC: 3142 AN: 39692

South Asian (SAS) AF: 0.186 AC: 16072 AN: 86206

European-Finnish (FIN) AF: 0.104 AC: 5548 AN: 53328

Middle Eastern (MID) AF: 0.162 AC: 934 AN: 5766

European-Non Finnish (NFE) AF: 0.0793 AC: 88109 AN: 1111472

Other (OTH) AF: 0.0919 AC: 5545 AN: 60354

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

African (AFR) AF: 0.0389 AC: 1614 AN: 41438

American (AMR) AF: 0.0847 AC: 1294 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 532 AN: 3468

East Asian (EAS) AF: 0.0848 AC: 437 AN: 5152

South Asian (SAS) AF: 0.175 AC: 838 AN: 4780

European-Finnish (FIN) AF: 0.109 AC: 1147 AN: 10540

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0805 AC: 5472 AN: 67948

Other (OTH) AF: 0.0933 AC: 197 AN: 2112

Alfa AF: 0.0843 Hom.: 1268

Bravo AF: 0.0710

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.80
PhyloP100		-1.1
PromoterAI		0.071	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2304973; hg19: chr17-4642222; COSMIC: COSV52641918; COSMIC: COSV52641918;