rs4778889

Variant names:

• chr15-81296654-T-C
• rs4778889
• NM_172217.5:c.1903-274T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 86 publications found

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

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	NM_172217.5	MANE Select	c.1903-274T>C		intron	N/A	NP_757366.2	Q14005-1
	IL16	NM_001352686.2		c.2056-274T>C		intron	N/A	NP_001339615.1
	IL16	NM_001438661.1		c.2044-274T>C		intron	N/A	NP_001425590.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	ENST00000683961.1	MANE Select	c.1903-274T>C		intron	N/A	ENSP00000508085.1	Q14005-1
	IL16	ENST00000302987.10	TSL:1	c.2044-274T>C		intron	N/A	ENSP00000302935.5	A0A8C8KBU6
	IL16	ENST00000909975.1		c.1903-274T>C		intron	N/A	ENSP00000580034.1

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

African (AFR) AF: 0.398 AC: 16464 AN: 41416

American (AMR) AF: 0.215 AC: 3285 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3466

East Asian (EAS) AF: 0.220 AC: 1135 AN: 5166

South Asian (SAS) AF: 0.142 AC: 684 AN: 4812

European-Finnish (FIN) AF: 0.0870 AC: 922 AN: 10596

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12803 AN: 67966

Other (OTH) AF: 0.243 AC: 513 AN: 2112

Alfa AF: 0.286 Hom.: 2159

Bravo AF: 0.262

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.41
PhyloP100		0.0020
PromoterAI		0.026	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4778889; hg19: chr15-81588995;