rs2280015

Variant names:

• chr10-8068975-G-A
• rs2280015
• NM_001002295.2:c.925-498G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-8068975-G-A
• chr10-8068975-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002295.2(GATA3):​c.925-498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,154 control chromosomes in the GnomAD database, including 3,156 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3156 hom., cov: 32)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.925-498G>A		intron_variant	Intron 4 of 5	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9	c.925-498G>A		intron_variant	Intron 4 of 5	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208.4	c.922-498G>A		intron_variant	Intron 4 of 5	1		ENSP00000341619.3
GATA3	ENST00000461472.1	c.443-498G>A		intron_variant	Intron 1 of 2	3		ENSP00000515407.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30558 AN: 152034 Hom.: 3155 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.201 AC: 30567 AN: 152154 Hom.: 3156 Cov.: 32 AF XY: 0.201 AC XY: 14920 AN XY: 74400

African (AFR) AF: 0.236 AC: 9786 AN: 41502

American (AMR) AF: 0.136 AC: 2087 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1358 AN: 5168

South Asian (SAS) AF: 0.199 AC: 960 AN: 4822

European-Finnish (FIN) AF: 0.223 AC: 2366 AN: 10588

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12475 AN: 67994

Other (OTH) AF: 0.191 AC: 404 AN: 2112

Alfa AF: 0.183 Hom.: 460

Bravo AF: 0.199

Asia WGS AF: 0.188 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.48
PhyloP100		0.37
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: rs2280015; hg19: chr10-8110938;