rs444762

chr10-8061297-A-Cchr10-8061297-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002295.2(GATA3):c.778+2456A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,036 control chromosomes in the GnomAD database, including 34,201 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 0.67 (34201 hom., cov: 32)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA3	NM_001002295.2	c.778+2456A>C		intron_variant		ENST00000379328.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA3	ENST00000379328.9	c.778+2456A>C		intron_variant		1	NM_001002295.2	A1
GATA3	ENST00000346208.4	c.778+2456A>C		intron_variant		1		P4
GATA3	ENST00000461472.1	c.443+2456A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101908 AN: 151918 Hom.: 34178 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.671 AC: 101975 AN: 152036 Hom.: 34201 Cov.: 32 AF XY: 0.669 AC XY: 49714 AN XY: 74332

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.665

Alfa AF: 0.678 Hom.: 6120

Bravo AF: 0.664

Asia WGS AF: 0.748 AC: 2602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.8
Dann	Benign	0.63

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: rs444762; hg19: chr10-8103260;