Variant 2-70229320-TAAAA-TAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_022173.4(TIA1):c.223-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,007,400 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 30)

Exomes 𝑓: 0.034 ( 0 hom. )

Consequence

TIA1
NM_022173.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.61

Variant links:

Genes affected

TIA1 (HGNC:11802): (TIA1 cytotoxic granule associated RNA binding protein) The product encoded by this gene is a member of a RNA-binding protein family and possesses nucleolytic activity against cytotoxic lymphocyte (CTL) target cells. It has been suggested that this protein may be involved in the induction of apoptosis as it preferentially recognizes poly(A) homopolymers and induces DNA fragmentation in CTL targets. The major granule-associated species is a 15-kDa protein that is thought to be derived from the carboxyl terminus of the 40-kDa product by proteolytic processing. Alternative splicing resulting in different isoforms has been found for this gene. [provided by RefSeq, May 2017]

TIA1 links:

C2orf42 (HGNC:):

C2orf42 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-70229320-TA-T is Benign according to our data. Variant chr2-70229320-TA-T is described in ClinVar as [Benign]. Clinvar id is 448689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0343 (29608/862280) while in subpopulation AMR AF= 0.0461 (1126/24444). AF 95% confidence interval is 0.0439. There are 0 homozygotes in gnomad4_exome. There are 14599 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 78 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIA1	NM_022173.4 linkuse as main transcript	c.223-3delT		splice_region_variant, intron_variant		ENST00000433529.7	NP_071505.2	P31483-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIA1	ENST00000433529.7 linkuse as main transcript	c.223-3delT		splice_region_variant, intron_variant		2	NM_022173.4	ENSP00000401371.2		P31483-1

Frequencies

GnomAD3 genomes

AF:

0.000538

AC:

AN:

145064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00110

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000397

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00145

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000350

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0343

AC:

29608

AN:

862280

Hom.:

Cov.:

AF XY:

0.0343

AC XY:

14599

AN XY:

426184

show subpopulations

Gnomad4 AFR exome

AF:

0.0318

Gnomad4 AMR exome

AF:

0.0461

Gnomad4 ASJ exome

AF:

0.0437

Gnomad4 EAS exome

AF:

0.0262

Gnomad4 SAS exome

AF:

0.0455

Gnomad4 FIN exome

AF:

0.0471

Gnomad4 NFE exome

AF:

0.0327

Gnomad4 OTH exome

AF:

0.0352

GnomAD4 genome

AF:

0.000537

AC:

AN:

145120

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

AN XY:

70472

show subpopulations

Gnomad4 AFR

AF:

0.000603

Gnomad4 AMR

AF:

0.00110

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000397

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00145

Gnomad4 NFE

AF:

0.000350

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 11, 2016

- -

TIA1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Welander distal myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 13, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over