rs4577037

Variant names:

• chr15-81304319-T-G
• rs4577037
• NM_172217.5:c.3420+669T>G

Variant summary

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

The NM_172217.5(IL16):​c.3420+669T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,224 control chromosomes in the GnomAD database, including 1,104 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 0.11 (1104 hom., cov: 32)
• Consequence: IL16 NM_172217.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 14 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]

ENSG00000271725 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL16	NM_172217.5	c.3420+669T>G		intron_variant	Intron 16 of 18	ENST00000683961.1	NP_757366.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL16	ENST00000683961.1	c.3420+669T>G		intron_variant	Intron 16 of 18		NM_172217.5	ENSP00000508085.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16493 AN: 152106 Hom.: 1100 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.0301

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.108 AC: 16511 AN: 152224 Hom.: 1104 Cov.: 32 AF XY: 0.104 AC XY: 7748 AN XY: 74440

African (AFR) AF: 0.178 AC: 7394 AN: 41502

American (AMR) AF: 0.120 AC: 1834 AN: 15300

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

East Asian (EAS) AF: 0.176 AC: 914 AN: 5182

South Asian (SAS) AF: 0.0601 AC: 290 AN: 4828

European-Finnish (FIN) AF: 0.0301 AC: 320 AN: 10616

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0775 AC: 5270 AN: 68008

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.115 Hom.: 508

Bravo AF: 0.121

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.66
PhyloP100		0.42
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: rs4577037; hg19: chr15-81596660;