rs859

Variant names:

• chr15-81308981-A-G
• rs859
• NM_172217.5:c.*183A>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.*183A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 517,678 control chromosomes in the GnomAD database, including 24,585 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 0.33 (9104 hom., cov: 33)
  • Exomes 𝑓: 0.28 (15481 hom.)
• Consequence: IL16 NM_172217.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563
• Publications: 43 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:):

STARD5 (HGNC:18065): (StAR related lipid transfer domain containing 5) Proteins containing a steroidogenic acute regulatory-related lipid transfer (START) domain are often involved in the trafficking of lipids and cholesterol between diverse intracellular membranes. This gene is a member of the StarD subfamily that encodes START-related lipid transfer proteins. The protein encoded by this gene is a cholesterol transporter and is also able to bind and transport other sterol-derived molecules related to the cholesterol/bile acid biosynthetic pathways such as 25-hydroxycholesterol. Its expression is upregulated during endoplasmic reticulum (ER) stress. The protein is thought to act as a cytosolic sterol transporter that moves cholesterol between intracellular membranes such as from the cytoplasm to the ER and from the ER to the Golgi apparatus. Alternative splicing of this gene produces multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL16	NM_172217.5	c.*183A>G		3_prime_UTR_variant	Exon 19 of 19	ENST00000683961.1	NP_757366.2
STARD5	NM_181900.3	c.*4275T>C		downstream_gene_variant		ENST00000302824.7	NP_871629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL16	ENST00000683961.1	c.*183A>G		3_prime_UTR_variant	Exon 19 of 19		NM_172217.5	ENSP00000508085.1
STARD5	ENST00000302824.7	c.*4275T>C		downstream_gene_variant		1	NM_181900.3	ENSP00000304032.6

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50693 AN: 152108 Hom.: 9089 Cov.: 33

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.282 AC: 103234 AN: 365452 Hom.: 15481 Cov.: 4 AF XY: 0.277 AC XY: 52806 AN XY: 190860

African (AFR) AF: 0.475 AC: 4454 AN: 9386

American (AMR) AF: 0.289 AC: 3209 AN: 11114

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 3591 AN: 11782

East Asian (EAS) AF: 0.429 AC: 10885 AN: 25368

South Asian (SAS) AF: 0.193 AC: 5619 AN: 29120

European-Finnish (FIN) AF: 0.285 AC: 8379 AN: 29438

Middle Eastern (MID) AF: 0.271 AC: 473 AN: 1748

European-Non Finnish (NFE) AF: 0.266 AC: 59857 AN: 225440

Other (OTH) AF: 0.307 AC: 6767 AN: 22056

GnomAD4 genome AF: 0.333 AC: 50746 AN: 152226 Hom.: 9104 Cov.: 33 AF XY: 0.330 AC XY: 24567 AN XY: 74456

African (AFR) AF: 0.470 AC: 19522 AN: 41516

American (AMR) AF: 0.290 AC: 4445 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3470

East Asian (EAS) AF: 0.466 AC: 2412 AN: 5176

South Asian (SAS) AF: 0.210 AC: 1015 AN: 4824

European-Finnish (FIN) AF: 0.283 AC: 3008 AN: 10614

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18178 AN: 68002

Other (OTH) AF: 0.331 AC: 700 AN: 2112

Alfa AF: 0.279 Hom.: 4027

Bravo AF: 0.343

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.94
DANN	Benign	0.69
PhyloP100		-0.56
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: rs859; hg19: chr15-81601322;