rs4778636

Variant names:

• chr15-81299298-G-A
• rs4778636
• NM_172217.5:c.2054-82G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000683961.1(IL16):​c.2054-82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 1,598,460 control chromosomes in the GnomAD database, including 8,664 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 (1555 hom., cov: 33)
  • Exomes 𝑓: 0.092 (7109 hom.)
• Consequence: IL16 ENST00000683961.1 intron
• Scores: Splicing: ADA: 0.00001420
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.95
• Publications: 29 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 = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000683961.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	NM_172217.5	MANE Select	c.2054-82G>A		intron	N/A	NP_757366.2
	IL16	NM_001352686.2		c.2207-82G>A		intron	N/A	NP_001339615.1
	IL16	NM_001438661.1		c.2195-82G>A		intron	N/A	NP_001425590.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	ENST00000683961.1	MANE Select	c.2054-82G>A		intron	N/A	ENSP00000508085.1
	IL16	ENST00000302987.10	TSL:1	c.2195-82G>A		intron	N/A	ENSP00000302935.5
	IL16	ENST00000394652.6	TSL:1	c.-50-82G>A		intron	N/A	ENSP00000378147.2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18821 AN: 152060 Hom.: 1548 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.100 AC: 23698 AN: 236642 AF XY: 0.0925

Gnomad AFR exome AF: 0.228

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.0540

Gnomad EAS exome AF: 0.183

Gnomad FIN exome AF: 0.0394

Gnomad NFE exome AF: 0.0814

Gnomad OTH exome AF: 0.0899

GnomAD4 exome AF: 0.0921 AC: 133259 AN: 1446282 Hom.: 7109 Cov.: 32 AF XY: 0.0897 AC XY: 64589 AN XY: 719926

African (AFR) AF: 0.234 AC: 7815 AN: 33432

American (AMR) AF: 0.141 AC: 6292 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0537 AC: 1402 AN: 26128

East Asian (EAS) AF: 0.181 AC: 7173 AN: 39684

South Asian (SAS) AF: 0.0537 AC: 4617 AN: 85990

European-Finnish (FIN) AF: 0.0453 AC: 1788 AN: 39488

Middle Eastern (MID) AF: 0.0590 AC: 340 AN: 5762

European-Non Finnish (NFE) AF: 0.0883 AC: 98051 AN: 1110852

Other (OTH) AF: 0.0960 AC: 5781 AN: 60234

GnomAD4 genome AF: 0.124 AC: 18848 AN: 152178 Hom.: 1555 Cov.: 33 AF XY: 0.119 AC XY: 8878 AN XY: 74406

African (AFR) AF: 0.229 AC: 9502 AN: 41476

American (AMR) AF: 0.130 AC: 1992 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3472

East Asian (EAS) AF: 0.176 AC: 911 AN: 5172

South Asian (SAS) AF: 0.0599 AC: 289 AN: 4828

European-Finnish (FIN) AF: 0.0303 AC: 322 AN: 10612

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0781 AC: 5314 AN: 68006

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.0945 Hom.: 1617

Bravo AF: 0.139

Asia WGS AF: 0.112 AC: 389 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	0.030
DANN	Benign	0.41
PhyloP100		-4.0
PromoterAI		0.0072	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.046
SpliceAI score (max)		0.010		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: rs4778636; hg19: chr15-81591639; COSMIC: COSV57260292; COSMIC: COSV57260292;