Genetic Variant TAL1:c.447-72G>C (chr1-47224170-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290403.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TAL1	NM_001290403.2	MANE Select	c.447-72G>C	intron	N/A	NP_001277332.1	P17542-1
TAL1	NM_001287347.2		c.447-72G>C	intron	N/A	NP_001274276.1	Q16509
TAL1	NM_001290404.1		c.447-72G>C	intron	N/A	NP_001277333.1	P17542-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TAL1	ENST00000691006.1	MANE Select	c.447-72G>C	intron	N/A	ENSP00000510655.1	P17542-1
TAL1	ENST00000294339.3	TSL:1	c.447-72G>C	intron	N/A	ENSP00000294339.3	P17542-1
TAL1	ENST00000371884.6	TSL:1	c.447-72G>C	intron	N/A	ENSP00000360951.1	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

African (AFR)

AF:

0.269

AC:

8326

AN:

30972

American (AMR)

AF:

0.382

AC:

16747

AN:

43884

Ashkenazi Jewish (ASJ)

AF:

0.637

AC:

15913

AN:

24974

East Asian (EAS)

AF:

0.00852

AC:

332

AN:

38948

South Asian (SAS)

AF:

0.473

AC:

39233

AN:

82950

European-Finnish (FIN)

AF:

0.639

AC:

32000

AN:

50110

Middle Eastern (MID)

AF:

0.622

AC:

2909

AN:

4674

European-Non Finnish (NFE)

AF:

0.593

AC:

594761

AN:

1003532

Other (OTH)

AF:

0.526

AC:

29550

AN:

56220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

15056

30112

45167

60223

75279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15262

30524

45786

61048

76310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.471

AC:

71578

AN:

151816

Hom.:

19127

Cov.:

AF XY:

0.469

AC XY:

34791

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.273

AC:

11295

AN:

41384

American (AMR)

AF:

0.436

AC:

6663

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.634

AC:

2197

AN:

3468

East Asian (EAS)

AF:

0.0174

AC:

AN:

5158

South Asian (SAS)

AF:

0.456

AC:

2191

AN:

4802

European-Finnish (FIN)

AF:

0.632

AC:

6664

AN:

10552

Middle Eastern (MID)

AF:

0.637

AC:

186

AN:

292

European-Non Finnish (NFE)

AF:

0.601

AC:

40784

AN:

67870

Other (OTH)

AF:

0.499

AC:

1052

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1673

3345

5018

6690

8363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.429

Hom.:

1406

Bravo

AF:

0.446

Asia WGS

AF:

0.266

AC:

927

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.9

(source)

DANN

Benign

0.62

PhyloP100

-0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over