rs3781093

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001002295.2(GATA3):​c.778+1123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,096 control chromosomes in the GnomAD database, including 3,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 3087 hom., cov: 33)

Consequence

GATA3
NM_001002295.2 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.464
Variant links:
Genes affected
GATA3 (HGNC:4172): (GATA binding protein 3) This gene encodes a protein which belongs to the GATA family of transcription factors. The protein contains two GATA-type zinc fingers and is an important regulator of T-cell development and plays an important role in endothelial cell biology. Defects in this gene are the cause of hypoparathyroidism with sensorineural deafness and renal dysplasia. [provided by RefSeq, Nov 2009]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 10-8059964-T-C is Benign according to our data. Variant chr10-8059964-T-C is described in ClinVar as [Benign]. Clinvar id is 3893658.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GATA3NM_001002295.2 linkc.778+1123T>C intron_variant Intron 3 of 5 ENST00000379328.9 NP_001002295.1 P23771-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GATA3ENST00000379328.9 linkc.778+1123T>C intron_variant Intron 3 of 5 1 NM_001002295.2 ENSP00000368632.3 P23771-2
GATA3ENST00000346208.4 linkc.778+1123T>C intron_variant Intron 3 of 5 1 ENSP00000341619.3 P23771-1
GATA3ENST00000461472.1 linkc.442+1123T>C intron_variant Intron 1 of 2 3 ENSP00000515407.1 A0A994J6H6

Frequencies

GnomAD3 genomes
AF:
0.193
AC:
29376
AN:
151978
Hom.:
3080
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.205
Gnomad AMI
AF:
0.274
Gnomad AMR
AF:
0.293
Gnomad ASJ
AF:
0.236
Gnomad EAS
AF:
0.304
Gnomad SAS
AF:
0.191
Gnomad FIN
AF:
0.212
Gnomad MID
AF:
0.236
Gnomad NFE
AF:
0.149
Gnomad OTH
AF:
0.199
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.193
AC:
29396
AN:
152096
Hom.:
3087
Cov.:
33
AF XY:
0.199
AC XY:
14792
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.204
AC:
0.204469
AN:
0.204469
Gnomad4 AMR
AF:
0.293
AC:
0.29327
AN:
0.29327
Gnomad4 ASJ
AF:
0.236
AC:
0.236175
AN:
0.236175
Gnomad4 EAS
AF:
0.305
AC:
0.30476
AN:
0.30476
Gnomad4 SAS
AF:
0.193
AC:
0.192516
AN:
0.192516
Gnomad4 FIN
AF:
0.212
AC:
0.212462
AN:
0.212462
Gnomad4 NFE
AF:
0.149
AC:
0.14911
AN:
0.14911
Gnomad4 OTH
AF:
0.196
AC:
0.196023
AN:
0.196023
Heterozygous variant carriers
0
1206
2412
3619
4825
6031
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
310
620
930
1240
1550
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.176
Hom.:
2174
Bravo
AF:
0.206
Asia WGS
AF:
0.213
AC:
740
AN:
3478

ClinVar

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

Submissions by phenotype

B-cell childhood acute lymphoblastic leukemia Benign:1
Nov 04, 2024
Genetics and Cancer Laboratory, National Institute of Pediatrics, Mexico
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:case-control

No clasiffication has been reported for this variant. However in the Mexican population, we have identified that the C allele was more frequent in children with acute lymphoblastic leukemia (ALL) than controls. In different populations this variant is associated with susceptibility to developing childhood ALL. We clearly observed that the C allele was associated with the risk of developing ALL in Mexican children. These results would be the first to demostrate the association between this variant and the disease in our country. Based on ACMG Guidelines 2015, this varians could be classified as BS1 (Allele frequency is greater than expected for disorder). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
3.2
DANN
Benign
0.48
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

Publications

LitVar

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

Other links and lift over

dbSNP: rs3781093; hg19: chr10-8101927; COSMIC: COSV60522152; COSMIC: COSV60522152; API