Variant 15-81273175-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_172217.5(IL16):c.761C>A(p.Ala254Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000555 in 1,460,080 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

IL16
NM_172217.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.67

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL16	NM_172217.5 linkuse as main transcript	c.761C>A	p.Ala254Glu	missense_variant	6/19	ENST00000683961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL16	ENST00000683961.1 linkuse as main transcript	c.761C>A	p.Ala254Glu	missense_variant	6/19		NM_172217.5	A2	Q14005-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000443

AC:

AN:

248540

Hom.:

AF XY:

0.0000371

AC XY:

AN XY:

134934

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000975

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000555

AC:

AN:

1460080

Hom.:

Cov.:

AF XY:

0.0000661

AC XY:

AN XY:

726388

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000693

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000489

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000331

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.761C>A (p.A254E) alteration is located in exon 5 (coding exon 5) of the IL16 gene. This alteration results from a C to A substitution at nucleotide position 761, causing the alanine (A) at amino acid position 254 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Uncertain

0.070

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;T

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Benign

-0.61

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.1

D;D;D

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.80, 0.82

MutPred

0.67

Gain of disorder (P = 0.046);Gain of disorder (P = 0.046);Gain of disorder (P = 0.046);

MVP

0.63

MPC

0.58

ClinPred

0.84

GERP RS

4.9

Varity_R

0.50

gMVP

0.76

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over