Variant 1-47219897-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001290403.2(TAL1):c.819C>T(p.Gly273Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 1,507,692 control chromosomes in the GnomAD database, including 1,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. G273G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.049 ( 198 hom., cov: 31)

Exomes 𝑓: 0.042 ( 1236 hom. )

Consequence

TAL1
NM_001290403.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.12

Variant links:

Genes affected

TAL1 (HGNC:11556): (TAL bHLH transcription factor 1, erythroid differentiation factor) Enables several functions, including DNA-binding transcription factor activity; E-box binding activity; and histone deacetylase binding activity. Involved in several processes, including myeloid cell differentiation; positive regulation of cellular component organization; and positive regulation of erythrocyte differentiation. Located in chromatin and nucleoplasm. Part of transcription regulator complex. Implicated in acute lymphoblastic leukemia. [provided by Alliance of Genome Resources, Apr 2022]

TAL1 links:

TAL1 (HGNC:):

TAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-47219897-G-A is Benign according to our data. Variant chr1-47219897-G-A is described in ClinVar as [Benign]. Clinvar id is 3056122.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAL1	NM_001290403.2 linkuse as main transcript	c.819C>T	p.Gly273Gly	synonymous_variant	5/5	ENST00000691006.1	NP_001277332.1	P17542-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TAL1	ENST00000691006.1 linkuse as main transcript	c.819C>T	p.Gly273Gly	synonymous_variant	5/5		NM_001290403.2	ENSP00000510655.1	P17542-1
TAL1	ENST00000294339.3 linkuse as main transcript	c.819C>T	p.Gly273Gly	synonymous_variant	4/4	1		ENSP00000294339.3	P17542-1
TAL1	ENST00000371884.6 linkuse as main transcript	c.819C>T	p.Gly273Gly	synonymous_variant	5/5	1		ENSP00000360951.1	P17542-1
TAL1	ENST00000459729.1 linkuse as main transcript	n.587C>T		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes

AF:

0.0489

AC:

7172

AN:

146718

Hom.:

195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0793

Gnomad AMI

AF:

0.0321

Gnomad AMR

AF:

0.0303

Gnomad ASJ

AF:

0.0434

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0768

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.0649

Gnomad NFE

AF:

0.0395

Gnomad OTH

AF:

0.0499

GnomAD3 exomes

AF:

0.0416

AC:

7747

AN:

186182

Hom.:

223

AF XY:

0.0446

AC XY:

4534

AN XY:

101686

show subpopulations

Gnomad AFR exome

AF:

0.0878

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.0447

Gnomad EAS exome

AF:

0.00213

Gnomad SAS exome

AF:

0.0883

Gnomad FIN exome

AF:

0.0276

Gnomad NFE exome

AF:

0.0393

Gnomad OTH exome

AF:

0.0443

GnomAD4 exome

AF:

0.0417

AC:

56749

AN:

1360866

Hom.:

1236

Cov.:

AF XY:

0.0429

AC XY:

28700

AN XY:

669284

show subpopulations

Gnomad4 AFR exome

AF:

0.0915

Gnomad4 AMR exome

AF:

0.0270

Gnomad4 ASJ exome

AF:

0.0456

Gnomad4 EAS exome

AF:

0.000891

Gnomad4 SAS exome

AF:

0.0865

Gnomad4 FIN exome

AF:

0.0271

Gnomad4 NFE exome

AF:

0.0393

Gnomad4 OTH exome

AF:

0.0434

GnomAD4 genome

AF:

0.0489

AC:

7187

AN:

146826

Hom.:

198

Cov.:

AF XY:

0.0490

AC XY:

3503

AN XY:

71500

show subpopulations

Gnomad4 AFR

AF:

0.0796

Gnomad4 AMR

AF:

0.0302

Gnomad4 ASJ

AF:

0.0434

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0767

Gnomad4 FIN

AF:

0.0277

Gnomad4 NFE

AF:

0.0395

Gnomad4 OTH

AF:

0.0513

Alfa

AF:

0.0417

Hom.:

Bravo

AF:

0.0519

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TAL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.2

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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