15-81285798-C-T

Variant names:

• chr15-81285798-C-T
• rs4072111
• NM_172217.5:c.1300C>T

Variant summary

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

The NM_172217.5(IL16):​c.1300C>T​(p.Pro434Ser) variant causes a missense change. The variant allele was found at a frequency of 0.127 in 1,613,642 control chromosomes in the GnomAD database, including 16,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1268 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14948 hom.)
• Consequence: IL16 NM_172217.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.77
• Publications: 84 publications found

Genes affected

IL16 (HGNC:5980): (interleukin 16) The protein encoded by this gene is a pleiotropic cytokine that functions as a chemoattractant, a modulator of T cell activation, and an inhibitor of HIV replication. The signaling process of this cytokine is mediated by CD4. The product of this gene undergoes proteolytic processing, which is found to yield two functional proteins. The cytokine function is exclusively attributed to the secreted C-terminal peptide, while the N-terminal product may play a role in cell cycle control. Caspase 3 is reported to be involved in the proteolytic processing of this protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017577112).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172217.5. 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
	IL16	NM_172217.5	MANE Select	c.1300C>T	p.Pro434Ser	missense	Exon 10 of 19	NP_757366.2	Q14005-1
	IL16	NM_001352686.2		c.1453C>T	p.Pro485Ser	missense	Exon 10 of 19	NP_001339615.1
	IL16	NM_001438661.1		c.1441C>T	p.Pro481Ser	missense	Exon 10 of 19	NP_001425590.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	ENST00000683961.1	MANE Select	c.1300C>T	p.Pro434Ser	missense	Exon 10 of 19	ENSP00000508085.1	Q14005-1
	IL16	ENST00000302987.10	TSL:1	c.1441C>T	p.Pro481Ser	missense	Exon 10 of 19	ENSP00000302935.5	A0A8C8KBU6
	IL16	ENST00000909975.1		c.1300C>T	p.Pro434Ser	missense	Exon 10 of 19	ENSP00000580034.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17055 AN: 152064 Hom.: 1263 Cov.: 32

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.166 AC: 41495 AN: 249466 AF XY: 0.169

Gnomad AFR exome AF: 0.0506

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.189

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.128 AC: 187419 AN: 1461456 Hom.: 14948 Cov.: 32 AF XY: 0.134 AC XY: 97114 AN XY: 727070

African (AFR) AF: 0.0507 AC: 1697 AN: 33472

American (AMR) AF: 0.291 AC: 13016 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2769 AN: 26130

East Asian (EAS) AF: 0.196 AC: 7797 AN: 39690

South Asian (SAS) AF: 0.308 AC: 26572 AN: 86222

European-Finnish (FIN) AF: 0.132 AC: 7068 AN: 53416

Middle Eastern (MID) AF: 0.0874 AC: 504 AN: 5768

European-Non Finnish (NFE) AF: 0.108 AC: 120248 AN: 1111672

Other (OTH) AF: 0.128 AC: 7748 AN: 60378

GnomAD4 genome AF: 0.112 AC: 17078 AN: 152186 Hom.: 1268 Cov.: 32 AF XY: 0.120 AC XY: 8913 AN XY: 74390

African (AFR) AF: 0.0557 AC: 2315 AN: 41544

American (AMR) AF: 0.176 AC: 2682 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1024 AN: 5176

South Asian (SAS) AF: 0.304 AC: 1463 AN: 4812

European-Finnish (FIN) AF: 0.141 AC: 1492 AN: 10568

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7437 AN: 68014

Other (OTH) AF: 0.103 AC: 218 AN: 2114

Alfa AF: 0.113 Hom.: 3852

Bravo AF: 0.110

TwinsUK AF: 0.112 AC: 417

ALSPAC AF: 0.108 AC: 418

ESP6500AA AF: 0.0523 AC: 214

ESP6500EA AF: 0.106 AC: 886

ExAC AF: 0.162 AC: 19558

Asia WGS AF: 0.278 AC: 965 AN: 3478

EpiCase AF: 0.107

EpiControl AF: 0.102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.082	T
Eigen	Benign	0.052
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		4.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.16
Sift	Benign	0.15	T
Sift4G	Benign	1.0	T
Polyphen		0.97	D
Vest4		0.38
MPC		0.35
ClinPred		0.016	T
GERP RS		5.2
Varity_R		0.078
gMVP		0.36
Mutation Taster		=97/3	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: rs4072111; hg19: chr15-81578139; COSMIC: COSV57261650;