10-119584077-T-C

Variant names:

• chr10-119584077-T-C
• rs10886515
• NM_003252.4:c.130-1520A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003252.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIAL1	NM_003252.4	MANE Select	c.130-1520A>G		intron	N/A	NP_003243.1
	TIAL1	NM_001033925.2		c.130-1469A>G		intron	N/A	NP_001029097.1
	TIAL1	NM_001323968.2		c.13-1469A>G		intron	N/A	NP_001310897.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIAL1	ENST00000436547.7	TSL:1 MANE Select	c.130-1520A>G		intron	N/A	ENSP00000394902.2
	TIAL1	ENST00000497671.5	TSL:1	n.130-1520A>G		intron	N/A	ENSP00000431009.1
	TIAL1	ENST00000369093.6	TSL:2	c.130-1469A>G		intron	N/A	ENSP00000358089.2

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

African (AFR) AF: 0.463 AC: 19192 AN: 41438

American (AMR) AF: 0.327 AC: 5005 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3470

East Asian (EAS) AF: 0.605 AC: 3129 AN: 5168

South Asian (SAS) AF: 0.368 AC: 1775 AN: 4824

European-Finnish (FIN) AF: 0.260 AC: 2752 AN: 10578

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19638 AN: 67988

Other (OTH) AF: 0.373 AC: 784 AN: 2104

Alfa AF: 0.302 Hom.: 10426

Bravo AF: 0.362

Asia WGS AF: 0.486 AC: 1688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.77
PhyloP100		0.092
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10886515; hg19: chr10-121343589;