15-81309441-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000302824.7(STARD5):​c.*3815A>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 0.322 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

STARD5
ENST00000302824.7 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.375
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons MANE Protein UniProt
IL16NM_172217.5 linkuse as main transcriptc.*643T>C 3_prime_UTR_variant 19/19 ENST00000683961.1 NP_757366.2
STARD5NM_181900.3 linkuse as main transcriptc.*3815A>G 3_prime_UTR_variant 6/6 ENST00000302824.7 NP_871629.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STARD5ENST00000302824.7 linkuse as main transcriptc.*3815A>G 3_prime_UTR_variant 6/61 NM_181900.3 ENSP00000304032 P1Q9NSY2-1
IL16ENST00000683961.1 linkuse as main transcriptc.*643T>C 3_prime_UTR_variant 19/19 NM_172217.5 ENSP00000508085 A2Q14005-1
ENST00000607019.1 linkuse as main transcript upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.322
AC:
48992
AN:
151996
Hom.:
7984
Cov.:
33
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 15, 2020This 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1131445; hg19: chr15-81601782; API