17-4738460-C-T

Variant names:

• chr17-4738460-C-T
• rs1050997
• NM_001386809.1:c.249G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001386809.1(CXCL16):​c.249G>A​(p.Gly83Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,612,134 control chromosomes in the GnomAD database, including 450,643 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 0.67 (35504 hom., cov: 32)
  • Exomes 𝑓: 0.75 (415139 hom.)
• Consequence: CXCL16 NM_001386809.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 24 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.669 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL16	NM_001386809.1	c.249G>A	p.Gly83Gly	synonymous_variant	Exon 3 of 6	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2	c.249G>A	p.Gly83Gly	synonymous_variant	Exon 3 of 5		NP_001094282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL16	ENST00000293778.12	c.249G>A	p.Gly83Gly	synonymous_variant	Exon 3 of 6	1	NM_001386809.1	ENSP00000293778.7
CXCL16	ENST00000574412.6	c.249G>A	p.Gly83Gly	synonymous_variant	Exon 3 of 5	1		ENSP00000459592.2
CXCL16	ENST00000573123.1	c.87G>A	p.Gly29Gly	synonymous_variant	Exon 2 of 3	2		ENSP00000460145.1
CXCL16	ENST00000575168.1	n.80G>A		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101752 AN: 151978 Hom.: 35479 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.715 AC: 179152 AN: 250528 AF XY: 0.720

Gnomad AFR exome AF: 0.442

Gnomad AMR exome AF: 0.689

Gnomad ASJ exome AF: 0.782

Gnomad EAS exome AF: 0.692

Gnomad FIN exome AF: 0.715

Gnomad NFE exome AF: 0.768

Gnomad OTH exome AF: 0.745

GnomAD4 exome AF: 0.752 AC: 1097333 AN: 1460038 Hom.: 415139 Cov.: 41 AF XY: 0.751 AC XY: 545476 AN XY: 726362

African (AFR) AF: 0.446 AC: 14896 AN: 33416

American (AMR) AF: 0.694 AC: 30925 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 20323 AN: 26112

East Asian (EAS) AF: 0.707 AC: 28026 AN: 39664

South Asian (SAS) AF: 0.679 AC: 58480 AN: 86124

European-Finnish (FIN) AF: 0.714 AC: 38145 AN: 53402

Middle Eastern (MID) AF: 0.719 AC: 4147 AN: 5764

European-Non Finnish (NFE) AF: 0.772 AC: 857825 AN: 1110664

Other (OTH) AF: 0.739 AC: 44566 AN: 60324

GnomAD4 genome AF: 0.669 AC: 101814 AN: 152096 Hom.: 35504 Cov.: 32 AF XY: 0.667 AC XY: 49550 AN XY: 74320

African (AFR) AF: 0.453 AC: 18778 AN: 41476

American (AMR) AF: 0.725 AC: 11076 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2695 AN: 3466

East Asian (EAS) AF: 0.708 AC: 3661 AN: 5172

South Asian (SAS) AF: 0.656 AC: 3158 AN: 4812

European-Finnish (FIN) AF: 0.710 AC: 7502 AN: 10568

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52544 AN: 67996

Other (OTH) AF: 0.709 AC: 1501 AN: 2116

Alfa AF: 0.724 Hom.: 31838

Bravo AF: 0.661

Asia WGS AF: 0.695 AC: 2419 AN: 3478

EpiCase AF: 0.771

EpiControl AF: 0.776

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.7
DANN	Benign	0.74
PhyloP100		-0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1050997; hg19: chr17-4641755; COSMIC: COSV52640620; COSMIC: COSV52640620;