17-4735189-T-C

Variant names:

• chr17-4735189-T-C
• rs1876444
• NM_001386809.1:c.621A>G

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.621A>G​(p.Pro207Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,613,558 control chromosomes in the GnomAD database, including 250,546 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 0.52 (20911 hom., cov: 32)
  • Exomes 𝑓: 0.56 (229635 hom.)
• Consequence: CXCL16 NM_001386809.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.78
• Publications: 25 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=-0.93).
• BP7: Synonymous conserved (PhyloP=-5.78 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386809.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL16	NM_001386809.1	MANE Select	c.621A>G	p.Pro207Pro	synonymous	Exon 4 of 6	NP_001373738.1
	CXCL16	NM_001100812.2		c.621A>G	p.Pro207Pro	synonymous	Exon 4 of 5	NP_001094282.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL16	ENST00000293778.12	TSL:1 MANE Select	c.621A>G	p.Pro207Pro	synonymous	Exon 4 of 6	ENSP00000293778.7
	CXCL16	ENST00000574412.6	TSL:1	c.621A>G	p.Pro207Pro	synonymous	Exon 4 of 5	ENSP00000459592.2
	CXCL16	ENST00000576153.5	TSL:2	c.204A>G	p.Pro68Pro	synonymous	Exon 2 of 4	ENSP00000501470.1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78574 AN: 151996 Hom.: 20888 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.563

GnomAD2 exomes AF: 0.564 AC: 141351 AN: 250504 AF XY: 0.567

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.609

Gnomad ASJ exome AF: 0.648

Gnomad EAS exome AF: 0.585

Gnomad FIN exome AF: 0.540

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.579

GnomAD4 exome AF: 0.559 AC: 816989 AN: 1461444 Hom.: 229635 Cov.: 55 AF XY: 0.562 AC XY: 408363 AN XY: 726986

African (AFR) AF: 0.385 AC: 12875 AN: 33474

American (AMR) AF: 0.610 AC: 27218 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 16734 AN: 26132

East Asian (EAS) AF: 0.578 AC: 22935 AN: 39690

South Asian (SAS) AF: 0.620 AC: 53461 AN: 86240

European-Finnish (FIN) AF: 0.536 AC: 28611 AN: 53388

Middle Eastern (MID) AF: 0.586 AC: 3381 AN: 5768

European-Non Finnish (NFE) AF: 0.556 AC: 617820 AN: 1111754

Other (OTH) AF: 0.562 AC: 33954 AN: 60370

GnomAD4 genome AF: 0.517 AC: 78653 AN: 152114 Hom.: 20911 Cov.: 32 AF XY: 0.520 AC XY: 38646 AN XY: 74352

African (AFR) AF: 0.383 AC: 15880 AN: 41506

American (AMR) AF: 0.605 AC: 9235 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2245 AN: 3472

East Asian (EAS) AF: 0.600 AC: 3110 AN: 5180

South Asian (SAS) AF: 0.607 AC: 2926 AN: 4824

European-Finnish (FIN) AF: 0.537 AC: 5673 AN: 10572

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37820 AN: 67972

Other (OTH) AF: 0.563 AC: 1189 AN: 2112

Alfa AF: 0.549 Hom.: 19268

Bravo AF: 0.517

Asia WGS AF: 0.621 AC: 2160 AN: 3478

EpiCase AF: 0.557

EpiControl AF: 0.567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.059
DANN	Benign	0.41
PhyloP100		-5.8
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: rs1876444; hg19: chr17-4638484; COSMIC: COSV53411281; COSMIC: COSV53411281;