rs7534271

chr1-47228309-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290403.2(TAL1):c.-2+887G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 177,046 control chromosomes in the GnomAD database, including 22,915 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (19614 hom., cov: 32)
  • Exomes 𝑓: 0.45 (3301 hom.)
• Consequence: TAL1 NM_001290403.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAL1	NM_001290403.2	c.-2+887G>C		intron_variant		ENST00000691006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAL1	ENST00000691006.1	c.-2+887G>C		intron_variant			NM_001290403.2	P1
	ENST00000422216.1	n.1595C>G		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72981 AN: 151906 Hom.: 19593 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.449 AC: 11233 AN: 25020 Hom.: 3301 Cov.: 0 AF XY: 0.453 AC XY: 5186 AN XY: 11446

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.467

Gnomad4 ASJ exome AF: 0.647

Gnomad4 EAS exome AF: 0.00241

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.594

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.480 AC: 73036 AN: 152026 Hom.: 19614 Cov.: 32 AF XY: 0.478 AC XY: 35484 AN XY: 74310

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.504

Alfa AF: 0.551 Hom.: 3009

Bravo AF: 0.455

Asia WGS AF: 0.270 AC: 942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.8
Dann	Benign	0.46

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: rs7534271; hg19: chr1-47693981;