rs12438640

Variant names:

• chr15-81223921-G-A
• rs12438640
• NM_172217.5:c.-101-1378G>A

Variant summary

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

The NM_172217.5(IL16):​c.-101-1378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,158 control chromosomes in the GnomAD database, including 1,981 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 0.14 (1981 hom., cov: 32)
• Consequence: IL16 NM_172217.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL16	NM_172217.5	c.-101-1378G>A		intron_variant	Intron 1 of 18	ENST00000683961.1	NP_757366.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL16	ENST00000683961.1	c.-101-1378G>A		intron_variant	Intron 1 of 18		NM_172217.5	ENSP00000508085.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21567 AN: 152040 Hom.: 1970 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.0938

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0970

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.142 AC: 21611 AN: 152158 Hom.: 1981 Cov.: 32 AF XY: 0.149 AC XY: 11094 AN XY: 74384

African (AFR) AF: 0.142 AC: 5903 AN: 41518

American (AMR) AF: 0.252 AC: 3857 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 325 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1910 AN: 5166

South Asian (SAS) AF: 0.316 AC: 1523 AN: 4820

European-Finnish (FIN) AF: 0.113 AC: 1191 AN: 10586

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0970 AC: 6598 AN: 68004

Other (OTH) AF: 0.129 AC: 273 AN: 2114

Alfa AF: 0.125 Hom.: 899

Bravo AF: 0.152

Asia WGS AF: 0.326 AC: 1132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.058
DANN	Benign	0.39
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12438640; hg19: chr15-81516262;