Genetic Variant IL16:p.Val232Leu (chr15-81273108-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_172217.5(IL16):c.694G>C(p.Val232Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,008 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V232A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IL16
NM_172217.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.44

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL16	NM_172217.5	MANE Select	c.694G>C	p.Val232Leu	missense	Exon 6 of 19	NP_757366.2	Q14005-1
IL16	NM_001352686.2		c.847G>C	p.Val283Leu	missense	Exon 6 of 19	NP_001339615.1
IL16	NM_001438661.1		c.835G>C	p.Val279Leu	missense	Exon 6 of 19	NP_001425590.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL16	ENST00000683961.1	MANE Select	c.694G>C	p.Val232Leu	missense	Exon 6 of 19	ENSP00000508085.1	Q14005-1
IL16	ENST00000302987.10	TSL:1	c.835G>C	p.Val279Leu	missense	Exon 6 of 19	ENSP00000302935.5	A0A8C8KBU6
IL16	ENST00000909975.1		c.694G>C	p.Val232Leu	missense	Exon 6 of 19	ENSP00000580034.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461008

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726842

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111436

Other (OTH)

AF:

0.00

AC:

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.1

PhyloP100

8.4

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-2.0

REVEL

Benign

0.22

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0080

Polyphen

0.99

Vest4

0.75

MutPred

0.54

Loss of ubiquitination at K235 (P = 0.1423)

MVP

0.46

MPC

0.50

ClinPred

0.98

GERP RS

4.9

Varity_R

0.37

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over