chr10-8062245-C-A

Variant names:

• chr10-8062245-C-A
• rs3824662
• NM_001002295.2:c.779-1748C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001002295.2(GATA3):​c.779-1748C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,898 control chromosomes in the GnomAD database, including 2,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.18 (2831 hom., cov: 32)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05
• Publications: 89 publications found

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]

GATA3 Gene-Disease associations (from GenCC):

• hypoparathyroidism-deafness-renal disease syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-8062245-C-A is Benign according to our data. Variant chr10-8062245-C-A is described in ClinVar as [Benign]. Clinvar id is 1223371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.779-1748C>A		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.779-1748C>A		intron_variant	Intron 3 of 5	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208.4	c.779-1751C>A		intron_variant	Intron 3 of 5	1		ENSP00000341619.3
GATA3	ENST00000461472.1	c.442+3404C>A		intron_variant	Intron 1 of 2	3		ENSP00000515407.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27039 AN: 151782 Hom.: 2825 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 27042 AN: 151898 Hom.: 2831 Cov.: 32 AF XY: 0.185 AC XY: 13719 AN XY: 74196

African (AFR) AF: 0.0990 AC: 4103 AN: 41438

American (AMR) AF: 0.294 AC: 4484 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3472

East Asian (EAS) AF: 0.295 AC: 1523 AN: 5166

South Asian (SAS) AF: 0.197 AC: 949 AN: 4814

European-Finnish (FIN) AF: 0.242 AC: 2529 AN: 10462

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11880 AN: 67952

Other (OTH) AF: 0.199 AC: 420 AN: 2112

Alfa AF: 0.180 Hom.: 9249

Bravo AF: 0.185

Asia WGS AF: 0.206 AC: 712 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

According to several reports the germline classificaction is Benign. However in the Mexican population, we have identified that the A 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 A 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). -

not provided Benign:1

Sep 10, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30859636, 23996088, 24141364, 24203929) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.54
DANN	Benign	0.50
PhyloP100		-1.1
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

Other links and lift over

dbSNP: rs3824662; hg19: chr10-8104208;