rs2250333

Variant names:

• chr17-4738774-A-G
• rs2250333
• NM_001386809.1:c.218+8T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-4738774-A-G
• chr17-4738774-A-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.218+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 1,612,772 control chromosomes in the GnomAD database, including 517,122 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 0.74 (42191 hom., cov: 32)
  • Exomes 𝑓: 0.80 (474931 hom.)
• Consequence: CXCL16 NM_001386809.1 splice_region, intron
• Scores: Splicing: ADA: 0.0001153
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 26 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL16	NM_001386809.1	c.218+8T>C		splice_region_variant, intron_variant	Intron 2 of 5	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2	c.218+8T>C		splice_region_variant, intron_variant	Intron 2 of 4		NP_001094282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL16	ENST00000293778.12	c.218+8T>C		splice_region_variant, intron_variant	Intron 2 of 5	1	NM_001386809.1	ENSP00000293778.7
CXCL16	ENST00000574412.6	c.218+8T>C		splice_region_variant, intron_variant	Intron 2 of 4	1		ENSP00000459592.2
CXCL16	ENST00000573123.1	c.56+8T>C		splice_region_variant, intron_variant	Intron 1 of 2	2		ENSP00000460145.1
CXCL16	ENST00000575168.1	n.-235T>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111881 AN: 152034 Hom.: 42148 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.857

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.766

GnomAD2 exomes AF: 0.762 AC: 190411 AN: 250032 AF XY: 0.764

Gnomad AFR exome AF: 0.551

Gnomad AMR exome AF: 0.723

Gnomad ASJ exome AF: 0.849

Gnomad EAS exome AF: 0.694

Gnomad FIN exome AF: 0.766

Gnomad NFE exome AF: 0.823

Gnomad OTH exome AF: 0.795

GnomAD4 exome AF: 0.804 AC: 1174427 AN: 1460620 Hom.: 474931 Cov.: 44 AF XY: 0.802 AC XY: 582889 AN XY: 726584

African (AFR) AF: 0.560 AC: 18713 AN: 33434

American (AMR) AF: 0.728 AC: 32401 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 22011 AN: 26098

East Asian (EAS) AF: 0.708 AC: 28091 AN: 39660

South Asian (SAS) AF: 0.692 AC: 59624 AN: 86166

European-Finnish (FIN) AF: 0.764 AC: 40820 AN: 53396

Middle Eastern (MID) AF: 0.788 AC: 4541 AN: 5760

European-Non Finnish (NFE) AF: 0.828 AC: 920425 AN: 1111292

Other (OTH) AF: 0.792 AC: 47801 AN: 60332

GnomAD4 genome AF: 0.736 AC: 111974 AN: 152152 Hom.: 42191 Cov.: 32 AF XY: 0.732 AC XY: 54443 AN XY: 74376

African (AFR) AF: 0.562 AC: 23331 AN: 41482

American (AMR) AF: 0.775 AC: 11848 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2917 AN: 3470

East Asian (EAS) AF: 0.710 AC: 3676 AN: 5174

South Asian (SAS) AF: 0.671 AC: 3232 AN: 4820

European-Finnish (FIN) AF: 0.761 AC: 8060 AN: 10596

Middle Eastern (MID) AF: 0.856 AC: 250 AN: 292

European-Non Finnish (NFE) AF: 0.828 AC: 56269 AN: 67996

Other (OTH) AF: 0.766 AC: 1621 AN: 2116

Alfa AF: 0.795 Hom.: 169333

Bravo AF: 0.730

Asia WGS AF: 0.714 AC: 2484 AN: 3478

EpiCase AF: 0.824

EpiControl AF: 0.827

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.2
DANN	Benign	0.74
PhyloP100		1.3
PromoterAI		-0.0068	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs2250333; hg19: chr17-4642069; COSMIC: COSV52640627; COSMIC: COSV52640627;