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GeneBe

1-47219897-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001290403.2(TAL1):c.819C>T(p.Gly273=) 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 (★). 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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.12
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.12 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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/exons MANE UniProt
TAL1NM_001290403.2 linkuse as main transcriptc.819C>T p.Gly273= synonymous_variant 5/5 ENST00000691006.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TAL1ENST00000691006.1 linkuse as main transcriptc.819C>T p.Gly273= synonymous_variant 5/5 NM_001290403.2 P1P17542-1
TAL1ENST00000294339.3 linkuse as main transcriptc.819C>T p.Gly273= synonymous_variant 4/41 P1P17542-1
TAL1ENST00000371884.6 linkuse as main transcriptc.819C>T p.Gly273= synonymous_variant 5/51 P1P17542-1
TAL1ENST00000459729.1 linkuse as main transcriptn.587C>T non_coding_transcript_exon_variant 3/31

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0489
AC:
7172
AN:
146718
Hom.:
195
Cov.:
31
show subpopulations
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
GnomAD3 exomes
AF:
0.0416
AC:
7747
AN:
186182
Hom.:
223
AF XY:
0.0446
AC XY:
4534
AN XY:
101686
show subpopulations
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 SAS exome
AF:
0.0883
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0915
Gnomad4 AMR exome
AF:
0.0270
Gnomad4 ASJ exome
AF:
0.0456
Gnomad4 EAS exome
AF:
0.000891
Gnomad4 SAS exome
AF:
0.0865
Gnomad4 FIN exome
AF:
0.0271
Gnomad4 NFE exome
AF:
0.0393
Gnomad4 OTH exome
AF:
0.0434
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0489
AC:
7187
AN:
146826
Hom.:
198
Cov.:
31
AF XY:
0.0490
AC XY:
3503
AN XY:
71500
show subpopulations
Gnomad4 AFR
AF:
0.0796
Gnomad4 AMR
AF:
0.0302
Gnomad4 ASJ
AF:
0.0434
Gnomad4 EAS
AF:
0.00193
Gnomad4 SAS
AF:
0.0767
Gnomad4 FIN
AF:
0.0277
Gnomad4 NFE
AF:
0.0395
Gnomad4 OTH
AF:
0.0513
Alfa
AF:
0.0417
Hom.:
35
Bravo
AF:
0.0519

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

TAL1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesSep 24, 2019This 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

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144117146; hg19: chr1-47685569; COSMIC: COSV53746555; COSMIC: COSV53746555; API