10-8051071-G-T

Variant names:

• chr10-8051071-G-T
• rs501764
• ENST00000420815.5:n.401+203C>A

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+203C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 528,742 control chromosomes in the GnomAD database, including 195,099 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 0.86 (56140 hom., cov: 28)
  • Exomes 𝑓: 0.86 (138959 hom.)
• Consequence: GATA3-AS1 ENST00000420815.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 43 publications found

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]

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

ENSG00000232638 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3-AS1	NR_024256.1	n.1593C>A		non_coding_transcript_exon_variant	Exon 2 of 2
GATA3	NM_001441115.1	c.-369-4216G>T		intron_variant	Intron 1 of 5		NP_001428044.1
GATA3	NM_001441116.1	c.-369-4216G>T		intron_variant	Intron 2 of 6		NP_001428045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA3-AS1	ENST00000420815.5	n.401+203C>A		intron_variant	Intron 2 of 2	1
GATA3-AS1	ENST00000438755.1	n.426+178C>A		intron_variant	Intron 2 of 2	1
GATA3-AS1	ENST00000355358.1	n.1593C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130097 AN: 151374 Hom.: 56089 Cov.: 28

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.862

GnomAD2 exomes AF: 0.867 AC: 207232 AN: 239144 AF XY: 0.866

Gnomad AFR exome AF: 0.921

Gnomad AMR exome AF: 0.919

Gnomad ASJ exome AF: 0.860

Gnomad EAS exome AF: 0.988

Gnomad FIN exome AF: 0.818

Gnomad NFE exome AF: 0.816

Gnomad OTH exome AF: 0.848

GnomAD4 exome AF: 0.856 AC: 322961 AN: 377260 Hom.: 138959 Cov.: 0 AF XY: 0.862 AC XY: 185127 AN XY: 214868

African (AFR) AF: 0.920 AC: 9324 AN: 10132

American (AMR) AF: 0.919 AC: 33076 AN: 36004

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 9904 AN: 11542

East Asian (EAS) AF: 0.990 AC: 12929 AN: 13066

South Asian (SAS) AF: 0.931 AC: 61344 AN: 65860

European-Finnish (FIN) AF: 0.821 AC: 26002 AN: 31676

Middle Eastern (MID) AF: 0.856 AC: 1723 AN: 2014

European-Non Finnish (NFE) AF: 0.812 AC: 154731 AN: 190500

Other (OTH) AF: 0.846 AC: 13928 AN: 16466

GnomAD4 genome AF: 0.860 AC: 130202 AN: 151482 Hom.: 56140 Cov.: 28 AF XY: 0.862 AC XY: 63766 AN XY: 73970

African (AFR) AF: 0.915 AC: 37842 AN: 41356

American (AMR) AF: 0.879 AC: 13416 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 3002 AN: 3468

East Asian (EAS) AF: 0.990 AC: 4940 AN: 4988

South Asian (SAS) AF: 0.941 AC: 4534 AN: 4818

European-Finnish (FIN) AF: 0.820 AC: 8620 AN: 10518

Middle Eastern (MID) AF: 0.812 AC: 237 AN: 292

European-Non Finnish (NFE) AF: 0.811 AC: 54949 AN: 67770

Other (OTH) AF: 0.863 AC: 1812 AN: 2100

Alfa AF: 0.826 Hom.: 203271

Bravo AF: 0.867

Asia WGS AF: 0.965 AC: 3346 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.7
DANN	Benign	0.55
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs501764; hg19: chr10-8093034;