dbSNP rs2070929: TAL1:c.*1785C>G (chr1-47217935-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001290403.2(TAL1):c.*1785C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 396,002 control chromosomes in the GnomAD database, including 16,589 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5151 hom., cov: 32)

Exomes 𝑓: 0.29 ( 11438 hom. )

Consequence

TAL1
NM_001290403.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAL1	NM_001290403.2 link	c.*1785C>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000691006.1	NP_001277332.1	P17542-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAL1	ENST00000691006.1 link	c.*1785C>G	3_prime_UTR_variant	Exon 5 of 5		NM_001290403.2	ENSP00000510655.1	P17542-1
TAL1	ENST00000294339.3 link	c.*1785C>G	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000294339.3	P17542-1
TAL1	ENST00000371884.6 link	c.*1785C>G	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000360951.1	P17542-1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38141

AN:

151982

Hom.:

5161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.313

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.265

GnomAD4 exome

AF:

0.291

AC:

70992

AN:

243902

Hom.:

11438

Cov.:

AF XY:

0.290

AC XY:

35899

AN XY:

123642

show subpopulations

African (AFR)

AF:

0.177

AC:

1267

AN:

7154

American (AMR)

AF:

0.222

AC:

1640

AN:

7374

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

2485

AN:

9204

East Asian (EAS)

AF:

0.547

AC:

12490

AN:

22820

South Asian (SAS)

AF:

0.346

AC:

751

AN:

2168

European-Finnish (FIN)

AF:

0.214

AC:

4393

AN:

20558

Middle Eastern (MID)

AF:

0.245

AC:

313

AN:

1278

European-Non Finnish (NFE)

AF:

0.274

AC:

43078

AN:

157092

Other (OTH)

AF:

0.281

AC:

4575

AN:

16254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2572

5144

7716

10288

12860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

244

488

732

976

1220

<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:

0.251

AC:

38118

AN:

152100

Hom.:

5151

Cov.:

AF XY:

0.251

AC XY:

18649

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.181

AC:

7515

AN:

41516

American (AMR)

AF:

0.237

AC:

3630

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

948

AN:

3472

East Asian (EAS)

AF:

0.514

AC:

2645

AN:

5150

South Asian (SAS)

AF:

0.313

AC:

1505

AN:

4810

European-Finnish (FIN)

AF:

0.211

AC:

2228

AN:

10578

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18654

AN:

67972

Other (OTH)

AF:

0.262

AC:

553

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1440

2879

4319

5758

7198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.256

Hom.:

661

Bravo

AF:

0.248

Asia WGS

AF:

0.370

AC:

1288

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.2

(source)

DANN

Benign

0.40

PhyloP100

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over