15-81265800-C-T

Variant names:

• chr15-81265800-C-T
• rs1898353811
• NM_172217.5:c.563C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_172217.5(IL16):​c.563C>T​(p.Ala188Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IL16 NM_172217.5 missense, splice_region
• Scores: Splicing: ADA: 0.001584
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.465

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034531116).
• BP6: Variant 15-81265800-C-T is Benign according to our data. Variant chr15-81265800-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3860098.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL16	NM_172217.5	c.563C>T	p.Ala188Val	missense_variant, splice_region_variant	Exon 4 of 19	ENST00000683961.1	NP_757366.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL16	ENST00000683961.1	c.563C>T	p.Ala188Val	missense_variant, splice_region_variant	Exon 4 of 19		NM_172217.5	ENSP00000508085.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457760 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724776

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 05, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.5
DANN	Benign	0.70
DEOGEN2	Benign	0.087	T;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.035	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.11	.;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.53	N;N;N
REVEL	Benign	0.017
Sift	Benign	0.42	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.0020, 0.0010	.;B;B
Vest4		0.051, 0.045
MutPred		0.15		Gain of methylation at K186 (P = 0.1321);Gain of methylation at K186 (P = 0.1321);Gain of methylation at K186 (P = 0.1321);
MVP		0.11
MPC		0.11
ClinPred		0.11	T
GERP RS		-6.7
Varity_R		0.030
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0016
dbscSNV1_RF	Benign	0.054
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

LitVar

Other links and lift over

dbSNP: rs1898353811; hg19: chr15-81558141; COSMIC: COSV57261335;