rs4778889

Positions:

• chr15-81296654-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172217.5(IL16):​c.1903-274T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,024 control chromosomes in the GnomAD database, including 5,179 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.

• Frequency: Genomes: 𝑓 0.24 (5179 hom., cov: 32)
• Consequence: IL16 NM_172217.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL16	NM_172217.5	c.1903-274T>C		intron_variant		ENST00000683961.1	NP_757366.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL16	ENST00000683961.1	c.1903-274T>C		intron_variant			NM_172217.5	ENSP00000508085	A2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36647 AN: 151906 Hom.: 5154 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0870

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.237

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.242 AC: 36715 AN: 152024 Hom.: 5179 Cov.: 32 AF XY: 0.232 AC XY: 17265 AN XY: 74320

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0870

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.243

Alfa AF: 0.241 Hom.: 1061

Bravo AF: 0.262

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs4778889; hg19: chr15-81588995;