Variant 1-47224170-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001290403.2(TAL1):c.447-72G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 1,488,080 control chromosomes in the GnomAD database, including 234,030 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 19127 hom., cov: 30)

Exomes 𝑓: 0.55 ( 214903 hom. )

Consequence

TAL1
NM_001290403.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.613

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-47224170-C-G is Benign according to our data. Variant chr1-47224170-C-G is described in ClinVar as [Benign]. Clinvar id is 1246151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.596 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.447-72G>C		intron_variant		ENST00000691006.1	NP_001277332.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
TAL1	ENST00000691006.1 linkuse as main transcript	c.447-72G>C	intron_variant		NM_001290403.2	ENSP00000510655	P1	P17542-1
TAL1	ENST00000294339.3 linkuse as main transcript	c.447-72G>C	intron_variant	1		ENSP00000294339	P1	P17542-1
TAL1	ENST00000371884.6 linkuse as main transcript	c.447-72G>C	intron_variant	1		ENSP00000360951	P1	P17542-1

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71527

AN:

151698

Hom.:

19110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.634

Gnomad EAS

AF:

0.0172

Gnomad SAS

AF:

0.454

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.601

Gnomad OTH

AF:

0.497

GnomAD4 exome

AF:

0.554

AC:

739771

AN:

1336264

Hom.:

214903

AF XY:

0.554

AC XY:

370914

AN XY:

669514

show subpopulations

Gnomad4 AFR exome

AF:

0.269

Gnomad4 AMR exome

AF:

0.382

Gnomad4 ASJ exome

AF:

0.637

Gnomad4 EAS exome

AF:

0.00852

Gnomad4 SAS exome

AF:

0.473

Gnomad4 FIN exome

AF:

0.639

Gnomad4 NFE exome

AF:

0.593

Gnomad4 OTH exome

AF:

0.526

GnomAD4 genome

AF:

0.471

AC:

71578

AN:

151816

Hom.:

19127

Cov.:

AF XY:

0.469

AC XY:

34791

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.436

Gnomad4 ASJ

AF:

0.634

Gnomad4 EAS

AF:

0.0174

Gnomad4 SAS

AF:

0.456

Gnomad4 FIN

AF:

0.632

Gnomad4 NFE

AF:

0.601

Gnomad4 OTH

AF:

0.499

Alfa

AF:

0.429

Hom.:

1406

Bravo

AF:

0.446

Asia WGS

AF:

0.266

AC:

927

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.9

DANN

Benign

0.62

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

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