Variant 2-70236169-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001351511.1(TIA1):c.-79C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00005 in 1,600,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

TIA1
NM_001351511.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.80

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:

TIA1 (HGNC:):

TIA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 2-70236169-G-A is Benign according to our data. Variant chr2-70236169-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 458839.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIA1	NM_022173.4 linkuse as main transcript	c.33C>T	p.Val11Val	synonymous_variant	2/13	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.33C>T	p.Val11Val	synonymous_variant	2/13	2	NM_022173.4	ENSP00000401371.2		P31483-1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000447

AC:

AN:

245818

Hom.:

AF XY:

0.0000526

AC XY:

AN XY:

132958

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000597

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000334

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000483

AC:

AN:

1448698

Hom.:

Cov.:

AF XY:

0.0000596

AC XY:

AN XY:

721212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.0000683

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000499

Gnomad4 OTH exome

AF:

0.0000668

GnomAD4 genome

AF:

0.0000658

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000447

Hom.:

Bravo

AF:

0.0000642

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Welander distal myopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.5

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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