1-47219924-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.792T>G(p.Ala264=) 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.096 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAL1 NM_001290403.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.151

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=-0.84).
• BP6: Variant 1-47219924-A-C is Benign according to our data. Variant chr1-47219924-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3034085.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.151 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAL1	NM_001290403.2	c.792T>G	p.Ala264=	synonymous_variant	5/5	ENST00000691006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAL1	ENST00000691006.1	c.792T>G	p.Ala264=	synonymous_variant	5/5		NM_001290403.2	P1
TAL1	ENST00000294339.3	c.792T>G	p.Ala264=	synonymous_variant	4/4	1		P1
TAL1	ENST00000371884.6	c.792T>G	p.Ala264=	synonymous_variant	5/5	1		P1
TAL1	ENST00000459729.1	n.560T>G		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4190 AN: 43556 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0959

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.0517

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.0100

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.120

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00306 AC: 1259 AN: 411940 Hom.: 0 Cov.: 13 AF XY: 0.00298 AC XY: 625 AN XY: 209556

Gnomad4 AFR exome AF: 0.0000880

Gnomad4 AMR exome AF: 0.000154

Gnomad4 ASJ exome AF: 0.000142

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00120

Gnomad4 FIN exome AF: 0.0644

Gnomad4 NFE exome AF: 0.000241

Gnomad4 OTH exome AF: 0.000474

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0962 AC: 4193 AN: 43598 Hom.: 0 Cov.: 0 AF XY: 0.0861 AC XY: 1892 AN XY: 21982

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.0545

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0183

Gnomad4 SAS AF: 0.0525

Gnomad4 FIN AF: 0.0586

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.117

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TAL1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 01, 2019

This variant is classified as likely 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	-0.84
Cadd	Benign	4.9
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1403207816; hg19: chr1-47685596;