1-47217935-G-C

Variant names:

• chr1-47217935-G-C
• rs2070929
• NM_001290403.2:c.*1785C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290403.2(TAL1):​c.*1785C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 396,002 control chromosomes in the GnomAD database, including 16,589 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 0.25 (5151 hom., cov: 32)
  • Exomes 𝑓: 0.29 (11438 hom.)
• Consequence: TAL1 NM_001290403.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290403.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAL1	NM_001290403.2	MANE Select	c.*1785C>G		3_prime_UTR	Exon 5 of 5	NP_001277332.1
	TAL1	NM_001287347.2		c.*1785C>G		3_prime_UTR	Exon 5 of 5	NP_001274276.1
	TAL1	NM_001290404.1		c.*1785C>G		3_prime_UTR	Exon 6 of 6	NP_001277333.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAL1	ENST00000691006.1	MANE Select	c.*1785C>G		3_prime_UTR	Exon 5 of 5	ENSP00000510655.1
	TAL1	ENST00000294339.3	TSL:1	c.*1785C>G		3_prime_UTR	Exon 4 of 4	ENSP00000294339.3
	TAL1	ENST00000371884.6	TSL:1	c.*1785C>G		3_prime_UTR	Exon 5 of 5	ENSP00000360951.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38141 AN: 151982 Hom.: 5161 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.291 AC: 70992 AN: 243902 Hom.: 11438 Cov.: 0 AF XY: 0.290 AC XY: 35899 AN XY: 123642

African (AFR) AF: 0.177 AC: 1267 AN: 7154

American (AMR) AF: 0.222 AC: 1640 AN: 7374

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 2485 AN: 9204

East Asian (EAS) AF: 0.547 AC: 12490 AN: 22820

South Asian (SAS) AF: 0.346 AC: 751 AN: 2168

European-Finnish (FIN) AF: 0.214 AC: 4393 AN: 20558

Middle Eastern (MID) AF: 0.245 AC: 313 AN: 1278

European-Non Finnish (NFE) AF: 0.274 AC: 43078 AN: 157092

Other (OTH) AF: 0.281 AC: 4575 AN: 16254

GnomAD4 genome AF: 0.251 AC: 38118 AN: 152100 Hom.: 5151 Cov.: 32 AF XY: 0.251 AC XY: 18649 AN XY: 74338

African (AFR) AF: 0.181 AC: 7515 AN: 41516

American (AMR) AF: 0.237 AC: 3630 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3472

East Asian (EAS) AF: 0.514 AC: 2645 AN: 5150

South Asian (SAS) AF: 0.313 AC: 1505 AN: 4810

European-Finnish (FIN) AF: 0.211 AC: 2228 AN: 10578

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18654 AN: 67972

Other (OTH) AF: 0.262 AC: 553 AN: 2112

Alfa AF: 0.256 Hom.: 661

Bravo AF: 0.248

Asia WGS AF: 0.370 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.40
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2070929; hg19: chr1-47683607;