chr1-47219897-G-A

Variant names:

• chr1-47219897-G-A
• rs144117146
• NM_001290403.2:c.819C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001290403.2(TAL1):​c.819C>T​(p.Gly273Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 1,507,692 control chromosomes in the GnomAD database, including 1,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. G273G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.049 (198 hom., cov: 31)
  • Exomes 𝑓: 0.042 (1236 hom.)
• Consequence: TAL1 NM_001290403.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.12

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-47219897-G-A is Benign according to our data. Variant chr1-47219897-G-A is described in ClinVar as [Benign]. Clinvar id is 3056122.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAL1	NM_001290403.2	c.819C>T	p.Gly273Gly	synonymous_variant	Exon 5 of 5	ENST00000691006.1	NP_001277332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAL1	ENST00000691006.1	c.819C>T	p.Gly273Gly	synonymous_variant	Exon 5 of 5		NM_001290403.2	ENSP00000510655.1
TAL1	ENST00000294339.3	c.819C>T	p.Gly273Gly	synonymous_variant	Exon 4 of 4	1		ENSP00000294339.3
TAL1	ENST00000371884.6	c.819C>T	p.Gly273Gly	synonymous_variant	Exon 5 of 5	1		ENSP00000360951.1
TAL1	ENST00000459729.1	n.587C>T		non_coding_transcript_exon_variant	Exon 3 of 3	1

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7172 AN: 146718 Hom.: 195 Cov.: 31

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.0321

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0434

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.0649

Gnomad NFE AF: 0.0395

Gnomad OTH AF: 0.0499

GnomAD2 exomes AF: 0.0416 AC: 7747 AN: 186182 AF XY: 0.0446

Gnomad AFR exome AF: 0.0878

Gnomad AMR exome AF: 0.0253

Gnomad ASJ exome AF: 0.0447

Gnomad EAS exome AF: 0.00213

Gnomad FIN exome AF: 0.0276

Gnomad NFE exome AF: 0.0393

Gnomad OTH exome AF: 0.0443

GnomAD4 exome AF: 0.0417 AC: 56749 AN: 1360866 Hom.: 1236 Cov.: 64 AF XY: 0.0429 AC XY: 28700 AN XY: 669284

Gnomad4 AFR exome AF: 0.0915 AC: 2865 AN: 31296

Gnomad4 AMR exome AF: 0.0270 AC: 1043 AN: 38686

Gnomad4 ASJ exome AF: 0.0456 AC: 979 AN: 21468

Gnomad4 EAS exome AF: 0.000891 AC: 33 AN: 37052

Gnomad4 SAS exome AF: 0.0865 AC: 6589 AN: 76134

Gnomad4 FIN exome AF: 0.0271 AC: 1274 AN: 46942

Gnomad4 NFE exome AF: 0.0393 AC: 41246 AN: 1050270

Gnomad4 Remaining exome AF: 0.0434 AC: 2399 AN: 55282

GnomAD4 genome AF: 0.0489 AC: 7187 AN: 146826 Hom.: 198 Cov.: 31 AF XY: 0.0490 AC XY: 3503 AN XY: 71500

Gnomad4 AFR AF: 0.0796 AC: 0.0795641 AN: 0.0795641

Gnomad4 AMR AF: 0.0302 AC: 0.0302335 AN: 0.0302335

Gnomad4 ASJ AF: 0.0434 AC: 0.0434272 AN: 0.0434272

Gnomad4 EAS AF: 0.00193 AC: 0.00193133 AN: 0.00193133

Gnomad4 SAS AF: 0.0767 AC: 0.0767474 AN: 0.0767474

Gnomad4 FIN AF: 0.0277 AC: 0.0277031 AN: 0.0277031

Gnomad4 NFE AF: 0.0395 AC: 0.039503 AN: 0.039503

Gnomad4 OTH AF: 0.0513 AC: 0.0512695 AN: 0.0512695

Alfa AF: 0.0430 Hom.: 38

Bravo AF: 0.0519

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

TAL1-related disorder Benign:1

Sep 24, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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	-0.79
CADD	Benign	4.2
DANN	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144117146; hg19: chr1-47685569; COSMIC: COSV53746555; COSMIC: COSV53746555;