15-81265800-C-A

Variant names:

• chr15-81265800-C-A
• rs1898353811
• NM_172217.5:c.563C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_172217.5(IL16):​c.563C>A​(p.Ala188Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A188V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL16 NM_172217.5 missense, splice_region
• Scores: Splicing: ADA: 0.00004297
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03060487).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	NM_172217.5	MANE Select	c.563C>A	p.Ala188Glu	missense splice_region	Exon 4 of 19	NP_757366.2	Q14005-1
	IL16	NM_001352686.2		c.716C>A	p.Ala239Glu	missense splice_region	Exon 4 of 19	NP_001339615.1
	IL16	NM_001438661.1		c.704C>A	p.Ala235Glu	missense splice_region	Exon 4 of 19	NP_001425590.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	ENST00000683961.1	MANE Select	c.563C>A	p.Ala188Glu	missense splice_region	Exon 4 of 19	ENSP00000508085.1	Q14005-1
	IL16	ENST00000302987.10	TSL:1	c.704C>A	p.Ala235Glu	missense splice_region	Exon 4 of 19	ENSP00000302935.5	A0A8C8KBU6
	IL16	ENST00000909975.1		c.563C>A	p.Ala188Glu	missense splice_region	Exon 4 of 19	ENSP00000580034.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.19
DANN	Benign	0.48
DEOGEN2	Benign	0.080	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.47
PrimateAI	Benign	0.36	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.044
Sift	Benign	0.68	T
Sift4G	Benign	1.0	T
Polyphen		0.24	B
Vest4		0.17
MutPred		0.17		Loss of catalytic residue at A188 (P = 0.0413)
MVP		0.10
MPC		0.14
ClinPred		0.084	T
GERP RS		-6.7
Varity_R		0.055
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000043
dbscSNV1_RF	Benign	0.070
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: rs1898353811; hg19: chr15-81558141;