Genetic Variant IL16:p.Pro434Ser (chr15-81285798-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1268 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14948 hom. )

Consequence

IL16
NM_172217.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.77

Variant links:

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]

IL16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL16	NM_172217.5 link	c.1300C>T	p.Pro434Ser	missense_variant	Exon 10 of 19	ENST00000683961.1	NP_757366.2	Q14005-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL16	ENST00000683961.1 link	c.1300C>T	p.Pro434Ser	missense_variant	Exon 10 of 19		NM_172217.5	ENSP00000508085.1		Q14005-1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17055

AN:

152064

Hom.:

1263

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.166

AC:

41495

AN:

249466

Hom.:

4701

AF XY:

0.169

AC XY:

22814

AN XY:

135354

show subpopulations

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 SAS exome

AF:

0.315

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.:

AF XY:

0.134

AC XY:

97114

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.0507

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.308

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.112

AC:

17078

AN:

152186

Hom.:

1268

Cov.:

AF XY:

0.120

AC XY:

8913

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0557

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.304

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.113

Hom.:

2745

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

T;.;T

Eigen

Benign

0.052

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

.;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

1.2

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.15

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.97, 0.96

.;D;D

Vest4

0.38, 0.18

MPC

0.35

ClinPred

0.016

GERP RS

5.2

Varity_R

0.078

gMVP

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over