rs2070929

Positions:

• chr1-47217935-G-C
• chr1-47217935-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TAL1	NM_001290403.2	c.*1785C>G		3_prime_UTR_variant	5/5	ENST00000691006.1	NP_001277332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAL1	ENST00000691006	c.*1785C>G		3_prime_UTR_variant	5/5		NM_001290403.2	ENSP00000510655.1
TAL1	ENST00000294339	c.*1785C>G		3_prime_UTR_variant	4/4	1		ENSP00000294339.3
TAL1	ENST00000371884	c.*1785C>G		3_prime_UTR_variant	5/5	1		ENSP00000360951.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38141 AN: 151982 Hom.: 5161 Cov.: 32

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.: 0 AF XY: 0.290 AC XY: 35899 AN XY: 123642

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.270

Gnomad4 EAS exome AF: 0.547

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.251 AC: 38118 AN: 152100 Hom.: 5151 Cov.: 32 AF XY: 0.251 AC XY: 18649 AN XY: 74338

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.262

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
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs2070929; hg19: chr1-47683607;