rs11556218

Positions:

• chr15-81305928-T-G

Variant summary

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

The NM_172217.5(IL16):​c.3441T>G​(p.Asn1147Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 1,613,540 control chromosomes in the GnomAD database, including 8,302 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.12 (1337 hom., cov: 33)
  • Exomes 𝑓: 0.091 (6965 hom.)
• Consequence: IL16 NM_172217.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032948256).
• 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.3441T>G	p.Asn1147Lys	missense_variant	17/19	ENST00000683961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL16	ENST00000683961.1	c.3441T>G	p.Asn1147Lys	missense_variant	17/19		NM_172217.5	A2
	ENST00000607019.1	n.62-2299A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17779 AN: 152166 Hom.: 1334 Cov.: 33

Gnomad AFR AF: 0.206

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: 0.0302

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.112

GnomAD3 exomes AF: 0.0964 AC: 24215 AN: 251204 Hom.: 1503 AF XY: 0.0894 AC XY: 12138 AN XY: 135774

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.0539

Gnomad EAS exome AF: 0.183

Gnomad SAS exome AF: 0.0517

Gnomad FIN exome AF: 0.0372

Gnomad NFE exome AF: 0.0811

Gnomad OTH exome AF: 0.0868

GnomAD4 exome AF: 0.0909 AC: 132794 AN: 1461256 Hom.: 6965 Cov.: 32 AF XY: 0.0887 AC XY: 64490 AN XY: 726976

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: 0.0880

Gnomad4 OTH exome AF: 0.0951

GnomAD4 genome AF: 0.117 AC: 17799 AN: 152284 Hom.: 1337 Cov.: 33 AF XY: 0.112 AC XY: 8372 AN XY: 74462

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.0597

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.0781

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0897 Hom.: 1557

Bravo AF: 0.131

TwinsUK AF: 0.0893 AC: 331

ALSPAC AF: 0.0864 AC: 333

ESP6500AA AF: 0.200 AC: 882

ESP6500EA AF: 0.0836 AC: 719

ExAC AF: 0.0967 AC: 11737

Asia WGS AF: 0.118 AC: 411 AN: 3478

EpiCase AF: 0.0783

EpiControl AF: 0.0795

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.060
DANN	Benign	0.77
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.80	T;T;T
MetaRNN	Benign	0.0033	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;.
MutationTaster	Benign	0.0096	P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.067	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.36	B;D;.
Vest4		0.28
MutPred		0.39		Gain of solvent accessibility (P = 0.0038);Gain of solvent accessibility (P = 0.0038);.;
MPC		0.21
ClinPred		0.048	T
GERP RS		-6.3
Varity_R		0.10
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs11556218; hg19: chr15-81598269; COSMIC: COSV57153970; COSMIC: COSV57153970;