NM_172217.5:c.*643T>C

Variant names:

• chr15-81309441-T-C
• rs1131445
• NM_172217.5:c.*643T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_172217.5(IL16):​c.*643T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,618 control chromosomes in the GnomAD database, including 8,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7995 hom., cov: 33)
  • Exomes 𝑓: 0.33 (31 hom.)
• Consequence: IL16 NM_172217.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.375

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]

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]

ENSG00000271725 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-81309441-T-C is Benign according to our data. Variant chr15-81309441-T-C is described in ClinVar as [Benign]. Clinvar id is 1261119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL16	NM_172217.5	c.*643T>C		3_prime_UTR_variant	Exon 19 of 19	ENST00000683961.1	NP_757366.2
STARD5	NM_181900.3	c.*3815A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000302824.7	NP_871629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL16	ENST00000683961.1	c.*643T>C		3_prime_UTR_variant	Exon 19 of 19		NM_172217.5	ENSP00000508085.1
STARD5	ENST00000302824	c.*3815A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_181900.3	ENSP00000304032.6

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48992 AN: 151996 Hom.: 7984 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.329 AC: 165 AN: 502 Hom.: 31 Cov.: 0 AF XY: 0.317 AC XY: 90 AN XY: 284

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.322 AC: 49045 AN: 152116 Hom.: 7995 Cov.: 33 AF XY: 0.318 AC XY: 23630 AN XY: 74376

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.351

Alfa AF: 0.334 Hom.: 11751

Bravo AF: 0.317

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24465869) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs1131445; hg19: chr15-81601782;