rs2277680

Variant names:

• chr17-4735268-G-A
• rs2277680
• NM_001386809.1:c.542C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100812.2(CXCL16):​c.542C>T​(p.Ala181Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,613,650 control chromosomes in the GnomAD database, including 158,490 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A181G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.42 (13611 hom., cov: 32)
  • Exomes 𝑓: 0.44 (144879 hom.)
• Consequence: CXCL16 NM_001100812.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655
• Publications: 61 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.6505287E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100812.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL16	NM_001386809.1	MANE Select	c.542C>T	p.Ala181Val	missense	Exon 4 of 6	NP_001373738.1
	CXCL16	NM_001100812.2		c.542C>T	p.Ala181Val	missense	Exon 4 of 5	NP_001094282.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL16	ENST00000293778.12	TSL:1 MANE Select	c.542C>T	p.Ala181Val	missense	Exon 4 of 6	ENSP00000293778.7
	CXCL16	ENST00000574412.6	TSL:1	c.542C>T	p.Ala181Val	missense	Exon 4 of 5	ENSP00000459592.2
	CXCL16	ENST00000886021.1		c.542C>T	p.Ala181Val	missense	Exon 4 of 6	ENSP00000556080.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63111 AN: 151936 Hom.: 13597 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.442

GnomAD2 exomes AF: 0.468 AC: 117332 AN: 250682 AF XY: 0.470

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.549

Gnomad ASJ exome AF: 0.466

Gnomad EAS exome AF: 0.581

Gnomad FIN exome AF: 0.453

Gnomad NFE exome AF: 0.428

Gnomad OTH exome AF: 0.465

GnomAD4 exome AF: 0.442 AC: 645763 AN: 1461596 Hom.: 144879 Cov.: 57 AF XY: 0.445 AC XY: 323886 AN XY: 727106

African (AFR) AF: 0.303 AC: 10129 AN: 33478

American (AMR) AF: 0.546 AC: 24388 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 12029 AN: 26130

East Asian (EAS) AF: 0.576 AC: 22856 AN: 39694

South Asian (SAS) AF: 0.552 AC: 47574 AN: 86254

European-Finnish (FIN) AF: 0.450 AC: 24026 AN: 53412

Middle Eastern (MID) AF: 0.457 AC: 2635 AN: 5764

European-Non Finnish (NFE) AF: 0.428 AC: 475577 AN: 1111828

Other (OTH) AF: 0.440 AC: 26549 AN: 60388

GnomAD4 genome AF: 0.415 AC: 63173 AN: 152054 Hom.: 13611 Cov.: 32 AF XY: 0.422 AC XY: 31367 AN XY: 74314

African (AFR) AF: 0.305 AC: 12672 AN: 41482

American (AMR) AF: 0.510 AC: 7795 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3470

East Asian (EAS) AF: 0.593 AC: 3063 AN: 5162

South Asian (SAS) AF: 0.540 AC: 2602 AN: 4822

European-Finnish (FIN) AF: 0.456 AC: 4816 AN: 10554

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29303 AN: 67982

Other (OTH) AF: 0.441 AC: 930 AN: 2110

Alfa AF: 0.436 Hom.: 44509

Bravo AF: 0.414

TwinsUK AF: 0.430 AC: 1595

ALSPAC AF: 0.442 AC: 1705

ESP6500AA AF: 0.313 AC: 1377

ESP6500EA AF: 0.437 AC: 3756

ExAC AF: 0.460 AC: 55866

Asia WGS AF: 0.567 AC: 1973 AN: 3478

EpiCase AF: 0.426

EpiControl AF: 0.439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.49
DANN	Benign	0.51
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.043	N
MetaRNN	Benign	0.000047	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.66
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.018
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.016
MPC		0.17
ClinPred		0.0083	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.11
Mutation Taster		=99/1	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: rs2277680; hg19: chr17-4638563; COSMIC: COSV53411293; COSMIC: COSV53411293;