1-47219921-A-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001290403.2(TAL1):c.795T>G(p.Gly265=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0095 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAL1 NM_001290403.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-47219921-A-C is Benign according to our data. Variant chr1-47219921-A-C is described in ClinVar as [Benign]. Clinvar id is 3033534.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAL1	NM_001290403.2	c.795T>G	p.Gly265=	synonymous_variant	5/5	ENST00000691006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAL1	ENST00000691006.1	c.795T>G	p.Gly265=	synonymous_variant	5/5		NM_001290403.2	P1
TAL1	ENST00000294339.3	c.795T>G	p.Gly265=	synonymous_variant	4/4	1		P1
TAL1	ENST00000371884.6	c.795T>G	p.Gly265=	synonymous_variant	5/5	1		P1
TAL1	ENST00000459729.1	n.563T>G		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5928 AN: 46772 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0733

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.0204

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.152

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00953 AC: 2104 AN: 220820 Hom.: 0 Cov.: 4 AF XY: 0.00901 AC XY: 1040 AN XY: 115370

Gnomad4 AFR exome AF: 0.00124

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.00114

Gnomad4 EAS exome AF: 0.000711

Gnomad4 SAS exome AF: 0.00444

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.00177

Gnomad4 OTH exome AF: 0.00238

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.127 AC: 5932 AN: 46822 Hom.: 0 Cov.: 0 AF XY: 0.116 AC XY: 2739 AN XY: 23516

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0732

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0547

Gnomad4 SAS AF: 0.0926

Gnomad4 FIN AF: 0.0830

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.149

Alfa AF: 0.0000843 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TAL1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.15
Dann	Benign	0.49

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: rs745723143; hg19: chr1-47685593;