chr15-81308999-G-T

Variant names:

• chr15-81308999-G-T
• rs11325
• NM_172217.5:c.*201G>T

Variant summary

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

The NM_172217.5(IL16):​c.*201G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 488,574 control chromosomes in the GnomAD database, including 9,820 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 0.22 (5102 hom., cov: 34)
  • Exomes 𝑓: 0.16 (4718 hom.)
• Consequence: IL16 NM_172217.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636
• Publications: 16 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL16	NM_172217.5	c.*201G>T		3_prime_UTR_variant	Exon 19 of 19	ENST00000683961.1	NP_757366.2
STARD5	NM_181900.3	c.*4257C>A		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.*201G>T		3_prime_UTR_variant	Exon 19 of 19		NM_172217.5	ENSP00000508085.1
STARD5	ENST00000302824.7	c.*4257C>A		downstream_gene_variant		1	NM_181900.3	ENSP00000304032.6

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34151 AN: 152128 Hom.: 5078 Cov.: 34

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0673

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.158 AC: 53151 AN: 336328 Hom.: 4718 Cov.: 3 AF XY: 0.155 AC XY: 27154 AN XY: 174658

African (AFR) AF: 0.422 AC: 3679 AN: 8728

American (AMR) AF: 0.211 AC: 2171 AN: 10312

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 2082 AN: 11168

East Asian (EAS) AF: 0.212 AC: 5175 AN: 24418

South Asian (SAS) AF: 0.133 AC: 3144 AN: 23554

European-Finnish (FIN) AF: 0.0858 AC: 2310 AN: 26934

Middle Eastern (MID) AF: 0.224 AC: 373 AN: 1666

European-Non Finnish (NFE) AF: 0.146 AC: 30395 AN: 208680

Other (OTH) AF: 0.183 AC: 3822 AN: 20868

GnomAD4 genome AF: 0.225 AC: 34225 AN: 152246 Hom.: 5102 Cov.: 34 AF XY: 0.218 AC XY: 16206 AN XY: 74446

African (AFR) AF: 0.428 AC: 17775 AN: 41514

American (AMR) AF: 0.199 AC: 3046 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3470

East Asian (EAS) AF: 0.215 AC: 1115 AN: 5186

South Asian (SAS) AF: 0.134 AC: 649 AN: 4826

European-Finnish (FIN) AF: 0.0673 AC: 714 AN: 10616

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9547 AN: 68016

Other (OTH) AF: 0.230 AC: 487 AN: 2116

Alfa AF: 0.180 Hom.: 3835

Bravo AF: 0.248

Asia WGS AF: 0.200 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.65
PhyloP100		-0.64
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: rs11325; hg19: chr15-81601340;