17-4734715-T-G

Variant names:

• chr17-4734715-T-G
• rs3744700
• NM_001386809.1:c.719-63A>C

Variant summary

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

The NM_001386809.1(CXCL16):​c.719-63A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,365,264 control chromosomes in the GnomAD database, including 323,322 homozygotes. 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: 𝑓 0.66 (34000 hom., cov: 31)
  • Exomes 𝑓: 0.69 (289322 hom.)
• Consequence: CXCL16 NM_001386809.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL16	NM_001386809.1	c.719-63A>C		intron_variant	Intron 4 of 5	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2	c.719-63A>C		intron_variant	Intron 4 of 4		NP_001094282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL16	ENST00000293778.12	c.719-63A>C		intron_variant	Intron 4 of 5	1	NM_001386809.1	ENSP00000293778.7
CXCL16	ENST00000574412.6	c.719-63A>C		intron_variant	Intron 4 of 4	1		ENSP00000459592.2
CXCL16	ENST00000576153.5	c.302-63A>C		intron_variant	Intron 2 of 3	2		ENSP00000501470.1
CXCL16	ENST00000575168.1	n.550-63A>C		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100915 AN: 151894 Hom.: 33985 Cov.: 31

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.672

GnomAD4 exome AF: 0.687 AC: 833205 AN: 1213252 Hom.: 289322 AF XY: 0.693 AC XY: 426679 AN XY: 616090

Gnomad4 AFR exome AF: 0.574

Gnomad4 AMR exome AF: 0.829

Gnomad4 ASJ exome AF: 0.677

Gnomad4 EAS exome AF: 0.869

Gnomad4 SAS exome AF: 0.872

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.656

Gnomad4 OTH exome AF: 0.678

GnomAD4 genome AF: 0.664 AC: 100970 AN: 152012 Hom.: 34000 Cov.: 31 AF XY: 0.676 AC XY: 50239 AN XY: 74314

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.671

Alfa AF: 0.667 Hom.: 47122

Bravo AF: 0.657

Asia WGS AF: 0.850 AC: 2955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.71

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: rs3744700; hg19: chr17-4638010;