15-81305928-T-G

Variant names:

• chr15-81305928-T-G
• rs11556218
• NM_172217.5:c.3441T>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.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. 15/21 in silico tools predict 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 (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
• Publications: 117 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 (MetaRNN=0.0032948256).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	NM_172217.5	MANE Select	c.3441T>G	p.Asn1147Lys	missense	Exon 17 of 19	NP_757366.2
	IL16	NM_001352686.2		c.3594T>G	p.Asn1198Lys	missense	Exon 17 of 19	NP_001339615.1
	IL16	NM_001438661.1		c.3582T>G	p.Asn1194Lys	missense	Exon 17 of 19	NP_001425590.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	ENST00000683961.1	MANE Select	c.3441T>G	p.Asn1147Lys	missense	Exon 17 of 19	ENSP00000508085.1
	IL16	ENST00000302987.10	TSL:1	c.3582T>G	p.Asn1194Lys	missense	Exon 17 of 19	ENSP00000302935.5
	IL16	ENST00000394652.6	TSL:1	c.1338T>G	p.Asn446Lys	missense	Exon 5 of 7	ENSP00000378147.2

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

GnomAD2 exomes AF: 0.0964 AC: 24215 AN: 251204 AF XY: 0.0894

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 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

African (AFR) AF: 0.213 AC: 7117 AN: 33450

American (AMR) AF: 0.141 AC: 6287 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0537 AC: 1403 AN: 26126

East Asian (EAS) AF: 0.181 AC: 7188 AN: 39696

South Asian (SAS) AF: 0.0536 AC: 4625 AN: 86250

European-Finnish (FIN) AF: 0.0427 AC: 2282 AN: 53418

Middle Eastern (MID) AF: 0.0602 AC: 347 AN: 5768

European-Non Finnish (NFE) AF: 0.0880 AC: 97802 AN: 1111446

Other (OTH) AF: 0.0951 AC: 5743 AN: 60380

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

African (AFR) AF: 0.206 AC: 8544 AN: 41548

American (AMR) AF: 0.125 AC: 1906 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3468

East Asian (EAS) AF: 0.176 AC: 913 AN: 5184

South Asian (SAS) AF: 0.0597 AC: 288 AN: 4822

European-Finnish (FIN) AF: 0.0302 AC: 321 AN: 10620

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0781 AC: 5315 AN: 68022

Other (OTH) AF: 0.110 AC: 233 AN: 2114

Alfa AF: 0.0945 Hom.: 3317

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 v4.9

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
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		-1.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.14
Sift	Benign	0.067	T
Sift4G	Benign	0.27	T
Polyphen		0.36	B
Vest4		0.28
MutPred		0.39		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
Mutation Taster		=86/14	polymorphism (auto)

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

Other links and lift over

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