rs3781093

Variant names:

• chr10-8059964-T-C
• rs3781093
• NM_001002295.2:c.778+1123T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.464

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]

ACMG classification

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
GATA3	NM_001002295.2	c.778+1123T>C		intron_variant	Intron 3 of 5	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9	c.778+1123T>C		intron_variant	Intron 3 of 5	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208.4	c.778+1123T>C		intron_variant	Intron 3 of 5	1		ENSP00000341619.3
GATA3	ENST00000461472.1	c.442+1123T>C		intron_variant	Intron 1 of 2	3		ENSP00000515407.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29376 AN: 151978 Hom.: 3080 Cov.: 33

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

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

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

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

Other links and lift over

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