1-47225448-G-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001290403.2(TAL1):c.441C>G(p.Leu147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,231,478 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (10 hom.)
• Consequence: TAL1 NM_001290403.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.596

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-47225448-G-C is Benign according to our data. Variant chr1-47225448-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 786986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.596 with no splicing effect.
• BS2: High AC in GnomAd at 574 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAL1	NM_001290403.2	c.441C>G	p.Leu147=	synonymous_variant	3/5	ENST00000691006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAL1	ENST00000691006.1	c.441C>G	p.Leu147=	synonymous_variant	3/5		NM_001290403.2	P1
TAL1	ENST00000294339.3	c.441C>G	p.Leu147=	synonymous_variant	2/4	1		P1
TAL1	ENST00000371884.6	c.441C>G	p.Leu147=	synonymous_variant	3/5	1		P1

Frequencies

GnomAD3 genomes AF: 0.00377 AC: 574 AN: 152174 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00755

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00844

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.00150 AC: 1621 AN: 1079196 Hom.: 10 Cov.: 32 AF XY: 0.00149 AC XY: 759 AN XY: 509756

Gnomad4 AFR exome AF: 0.00854

Gnomad4 AMR exome AF: 0.00924

Gnomad4 ASJ exome AF: 0.00757

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00117

Gnomad4 OTH exome AF: 0.00305

GnomAD4 genome AF: 0.00378 AC: 575 AN: 152282 Hom.: 4 Cov.: 33 AF XY: 0.00345 AC XY: 257 AN XY: 74448

Gnomad4 AFR AF: 0.00755

Gnomad4 AMR AF: 0.00843

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00137

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00409 Hom.: 1

Bravo AF: 0.00504

Asia WGS AF: 0.00174 AC: 6 AN: 3464

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	TAL1: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jun 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	2.0
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs537427396; hg19: chr1-47691120;