rs1876444

Positions:

• chr17-4735189-T-A
• chr17-4735189-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001386809.1(CXCL16):​c.621A>T​(p.Pro207=) variant causes a synonymous 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. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.78

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-5.78 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL16	NM_001386809.1	c.621A>T	p.Pro207=	synonymous_variant	4/6	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2	c.621A>T	p.Pro207=	synonymous_variant	4/5		NP_001094282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL16	ENST00000293778.12	c.621A>T	p.Pro207=	synonymous_variant	4/6	1	NM_001386809.1	ENSP00000293778	P1
CXCL16	ENST00000574412.6	c.621A>T	p.Pro207=	synonymous_variant	4/5	1		ENSP00000459592	P1
CXCL16	ENST00000576153.5	c.204A>T	p.Pro68=	synonymous_variant	2/4	2		ENSP00000501470
CXCL16	ENST00000575168.1	n.452A>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.051
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs1876444; hg19: chr17-4638484;