1-47224059-G-C

Variant names:

• chr1-47224059-G-C
• rs41289394
• NM_001290403.2:c.486C>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001290403.2(TAL1):​c.486C>G​(p.Thr162Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,613,808 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: TAL1 NM_001290403.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.33

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 1-47224059-G-C is Benign according to our data. Variant chr1-47224059-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3045332.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.33 with no splicing effect.
• BS2: High AC in GnomAd4 at 129 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAL1	NM_001290403.2	c.486C>G	p.Thr162Thr	synonymous_variant	Exon 4 of 5	ENST00000691006.1	NP_001277332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAL1	ENST00000691006.1	c.486C>G	p.Thr162Thr	synonymous_variant	Exon 4 of 5		NM_001290403.2	ENSP00000510655.1
TAL1	ENST00000294339.3	c.486C>G	p.Thr162Thr	synonymous_variant	Exon 3 of 4	1		ENSP00000294339.3
TAL1	ENST00000371884.6	c.486C>G	p.Thr162Thr	synonymous_variant	Exon 4 of 5	1		ENSP00000360951.1
TAL1	ENST00000459729.1	n.18C>G		non_coding_transcript_exon_variant	Exon 1 of 3	1

Frequencies

GnomAD3 genomes AF: 0.000848 AC: 129 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000844 AC: 212 AN: 251328 Hom.: 0 AF XY: 0.000898 AC XY: 122 AN XY: 135834

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.00167

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00113 AC: 1646 AN: 1461716 Hom.: 1 Cov.: 31 AF XY: 0.00106 AC XY: 772 AN XY: 727174

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.00141

Gnomad4 OTH exome AF: 0.000927

GnomAD4 genome AF: 0.000848 AC: 129 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.000700 AC XY: 52 AN XY: 74272

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00169

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.00138 Hom.: 0

Bravo AF: 0.000929

EpiCase AF: 0.00164

EpiControl AF: 0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TAL1-related disorder Benign:1

Mar 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	-0.63
CADD	Benign	8.1
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs41289394; hg19: chr1-47689731;