rs1803275

chr15-81306075-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_172217.5(IL16):c.3588G>A(p.Arg1196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0934 in 1,614,078 control chromosomes in the GnomAD database, including 8,280 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 0.12 (1328 hom., cov: 33)
  • Exomes 𝑓: 0.091 (6952 hom.)
• Consequence: IL16 NM_172217.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=1.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL16	NM_172217.5	c.3588G>A	p.Arg1196=	synonymous_variant	17/19	ENST00000683961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL16	ENST00000683961.1	c.3588G>A	p.Arg1196=	synonymous_variant	17/19		NM_172217.5	A2
	ENST00000607019.1	n.62-2446C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17750 AN: 152128 Hom.: 1325 Cov.: 33

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0597

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.111

GnomAD3 exomes AF: 0.0964 AC: 24222 AN: 251352 Hom.: 1499 AF XY: 0.0894 AC XY: 12139 AN XY: 135852

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.0538

Gnomad EAS exome AF: 0.182

Gnomad SAS exome AF: 0.0517

Gnomad FIN exome AF: 0.0371

Gnomad NFE exome AF: 0.0812

Gnomad OTH exome AF: 0.0868

GnomAD4 exome AF: 0.0910 AC: 133019 AN: 1461832 Hom.: 6952 Cov.: 32 AF XY: 0.0888 AC XY: 64572 AN XY: 727232

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.0537

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.0536

Gnomad4 FIN exome AF: 0.0427

Gnomad4 NFE exome AF: 0.0881

Gnomad4 OTH exome AF: 0.0952

GnomAD4 genome AF: 0.117 AC: 17770 AN: 152246 Hom.: 1328 Cov.: 33 AF XY: 0.112 AC XY: 8361 AN XY: 74434

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.0597

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0781

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0876 Hom.: 867

Bravo AF: 0.131

Asia WGS AF: 0.118 AC: 411 AN: 3478

EpiCase AF: 0.0782

EpiControl AF: 0.0794

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	8.9
Dann	Benign	0.51

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: rs1803275; hg19: chr15-81598416; COSMIC: COSV57155272; COSMIC: COSV57155272;