1-47225320-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.446+123G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 934,338 control chromosomes in the GnomAD database, including 52,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (12959 hom., cov: 32)
  • Exomes 𝑓: 0.31 (39986 hom.)
• Consequence: TAL1 NM_001290403.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.744

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=-0.89).
• BP6: Variant 1-47225320-C-G is Benign according to our data. Variant chr1-47225320-C-G is described in ClinVar as [Benign]. Clinvar id is 1286924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAL1	NM_001290403.2	c.446+123G>C		intron_variant		ENST00000691006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAL1	ENST00000691006.1	c.446+123G>C		intron_variant			NM_001290403.2	P1
TAL1	ENST00000294339.3	c.446+123G>C		intron_variant		1		P1
TAL1	ENST00000371884.6	c.446+123G>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58307 AN: 151958 Hom.: 12946 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.306 AC: 239465 AN: 782264 Hom.: 39986 AF XY: 0.306 AC XY: 114603 AN XY: 375104

Gnomad4 AFR exome AF: 0.608

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.384 AC: 58345 AN: 152074 Hom.: 12959 Cov.: 32 AF XY: 0.383 AC XY: 28503 AN XY: 74334

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.354

Alfa AF: 0.153 Hom.: 222

Bravo AF: 0.395

Asia WGS AF: 0.547 AC: 1901 AN: 3474

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.6
Dann	Benign	0.52
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8

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: rs2181222; hg19: chr1-47690992;