10-119584077-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003252.4(TIAL1):c.130-1520A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,056 control chromosomes in the GnomAD database, including 10,172 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 0.35 (10172 hom., cov: 32)
• Consequence: TIAL1 NM_003252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

Genes affected

TIAL1 (HGNC:11804): (TIA1 cytotoxic granule associated RNA binding protein like 1) The protein encoded by this gene is a member of a family of RNA-binding proteins, has three RNA recognition motifs (RRMs), and binds adenine and uridine-rich elements in mRNA and pre-mRNAs of a wide range of genes. It regulates various activities including translational control, splicing and apoptosis. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The different isoforms have been show to function differently with respect to post-transcriptional silencing. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIAL1	NM_003252.4	c.130-1520A>G		intron_variant		ENST00000436547.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIAL1	ENST00000436547.7	c.130-1520A>G		intron_variant		1	NM_003252.4	P1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53648 AN: 151938 Hom.: 10150 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.353 AC: 53727 AN: 152056 Hom.: 10172 Cov.: 32 AF XY: 0.352 AC XY: 26159 AN XY: 74334

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.373

Alfa AF: 0.301 Hom.: 9106

Bravo AF: 0.362

Asia WGS AF: 0.486 AC: 1688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.3
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10886515; hg19: chr10-121343589;