ENST00000420815.5:n.401+52A>G

Variant names:

• chr10-8051222-T-C
• rs485411
• ENST00000420815.5:n.401+52A>G

Variant summary

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

The ENST00000420815.5(GATA3-AS1):​n.401+52A>G variant causes a intron 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 ENST00000420815.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 28 publications found

Genes affected

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

ENSG00000232638 (HGNC:):

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=-0.84).
• 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 rank	MANE	Protein	UniProt
GATA3-AS1	NR_024256.1	n.1442A>G		non_coding_transcript_exon_variant	Exon 2 of 2
GATA3-AS1	NR_104329.1	n.502A>G		non_coding_transcript_exon_variant	Exon 2 of 3
GATA3	NM_001441115.1	c.-369-4065T>C		intron_variant	Intron 1 of 5		NP_001428044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA3-AS1	ENST00000420815.5	n.401+52A>G		intron_variant	Intron 2 of 2	1
GATA3-AS1	ENST00000438755.1	n.426+27A>G		intron_variant	Intron 2 of 2	1
GATA3-AS1	ENST00000355358.1	n.1442A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

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

GnomAD2 exomes AF: 0.809 AC: 96364 AN: 119052 AF XY: 0.813

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 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

African (AFR) AF: 0.881 AC: 5519 AN: 6266

American (AMR) AF: 0.861 AC: 19088 AN: 22170

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 5957 AN: 7460

East Asian (EAS) AF: 0.953 AC: 7023 AN: 7372

South Asian (SAS) AF: 0.891 AC: 44881 AN: 50364

European-Finnish (FIN) AF: 0.740 AC: 19784 AN: 26726

Middle Eastern (MID) AF: 0.795 AC: 928 AN: 1168

European-Non Finnish (NFE) AF: 0.743 AC: 95324 AN: 128320

Other (OTH) AF: 0.785 AC: 9088 AN: 11576

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

African (AFR) AF: 0.877 AC: 36358 AN: 41442

American (AMR) AF: 0.826 AC: 12617 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 2809 AN: 3472

East Asian (EAS) AF: 0.953 AC: 4878 AN: 5118

South Asian (SAS) AF: 0.903 AC: 4359 AN: 4826

European-Finnish (FIN) AF: 0.736 AC: 7716 AN: 10490

Middle Eastern (MID) AF: 0.745 AC: 216 AN: 290

European-Non Finnish (NFE) AF: 0.742 AC: 50458 AN: 67958

Other (OTH) AF: 0.800 AC: 1687 AN: 2108

Alfa AF: 0.765 Hom.: 92214

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
PhyloP100		-0.57

Splicing

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

Other links and lift over

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