1-47224170-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.613

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 -14 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_single_submitter, 1 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	UniProt
TAL1	NM_001290403.2	c.447-72G>C		intron_variant		ENST00000691006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAL1	ENST00000691006.1	c.447-72G>C		intron_variant			NM_001290403.2	P1
TAL1	ENST00000294339.3	c.447-72G>C		intron_variant		1		P1
TAL1	ENST00000371884.6	c.447-72G>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71527 AN: 151698 Hom.: 19110 Cov.: 30

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

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.: 30 AF XY: 0.469 AC XY: 34791 AN XY: 74204

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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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

Other links and lift over

dbSNP: rs34087210; hg19: chr1-47689842; COSMIC: COSV53746974; COSMIC: COSV53746974;