17-4738774-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001386809.1(CXCL16):​c.218+8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CXCL16 NM_001386809.1 splice_region, intron
• Scores: Splicing: ADA: 0.0001319
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL16	NM_001386809.1	c.218+8T>A		splice_region_variant, intron_variant	Intron 2 of 5	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2	c.218+8T>A		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>A		splice_region_variant, intron_variant	Intron 2 of 5	1	NM_001386809.1	ENSP00000293778.7
CXCL16	ENST00000574412.6	c.218+8T>A		splice_region_variant, intron_variant	Intron 2 of 4	1		ENSP00000459592.2
CXCL16	ENST00000573123.1	c.56+8T>A		splice_region_variant, intron_variant	Intron 1 of 2	2		ENSP00000460145.1
CXCL16	ENST00000575168.1	n.-235T>A		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.84
PhyloP100		1.3
PromoterAI		0.0014	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
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;