10-8051222-T-C

Variant summary

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

The NR_024256.1(GATA3-AS1):n.1442A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 413,316 control chromosomes in the GnomAD database, including 132,646 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 0.80 (49239 hom., cov: 32)
  • Exomes 𝑓: 0.79 (83407 hom.)
• Consequence: GATA3-AS1 NR_024256.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572

Genes affected

GATA3-AS1 (HGNC:33786): (GATA3 antisense RNA 1)

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA3-AS1	NR_024256.1	n.1442A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA3-AS1	ENST00000355358.1	n.1442A>G		non_coding_transcript_exon_variant	2/2	2
GATA3-AS1	ENST00000420815.5	n.401+52A>G		intron_variant, non_coding_transcript_variant		1
GATA3-AS1	ENST00000438755.1	n.426+27A>G		intron_variant, non_coding_transcript_variant		1
GATA3	ENST00000643001.1	c.-369-4065T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.803 AC: 121812 AN: 151776 Hom.: 49198 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.799

GnomAD3 exomes AF: 0.809 AC: 96364 AN: 119052 Hom.: 39393 AF XY: 0.813 AC XY: 50867 AN XY: 62602

Gnomad AFR exome AF: 0.887

Gnomad AMR exome AF: 0.860

Gnomad ASJ exome AF: 0.806

Gnomad EAS exome AF: 0.952

Gnomad SAS exome AF: 0.887

Gnomad FIN exome AF: 0.738

Gnomad NFE exome AF: 0.750

Gnomad OTH exome AF: 0.788

GnomAD4 exome AF: 0.794 AC: 207592 AN: 261422 Hom.: 83407 Cov.: 0 AF XY: 0.805 AC XY: 117112 AN XY: 145528

Gnomad4 AFR exome AF: 0.881

Gnomad4 AMR exome AF: 0.861

Gnomad4 ASJ exome AF: 0.799

Gnomad4 EAS exome AF: 0.953

Gnomad4 SAS exome AF: 0.891

Gnomad4 FIN exome AF: 0.740

Gnomad4 NFE exome AF: 0.743

Gnomad4 OTH exome AF: 0.785

GnomAD4 genome AF: 0.803 AC: 121910 AN: 151894 Hom.: 49239 Cov.: 32 AF XY: 0.806 AC XY: 59785 AN XY: 74194

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.809

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.800

Alfa AF: 0.762 Hom.: 67270

Bravo AF: 0.813

Asia WGS AF: 0.920 AC: 3194 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.2
Dann	Benign	0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs485411; hg19: chr10-8093185; COSMIC: COSV60522064;