10-8051071-G-T

Position:

• chr10-8051071-G-T

Variant summary

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

The ENST00000643001.1(GATA3):​c.-369-4216G>T 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 ENST00000643001.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

Genes affected

GATA3-AS1 (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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GATA3	XM_005252443.6	c.-369-4216G>T		intron_variant			XP_005252500.1
GATA3	XM_047425045.1	c.-369-4216G>T		intron_variant			XP_047281001.1
GATA3-AS1	NR_024256.1	n.1593C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA3-AS1	ENST00000420815.5	n.401+203C>A		intron_variant		1
GATA3-AS1	ENST00000438755.1	n.426+178C>A		intron_variant		1
GATA3	ENST00000643001.1	c.-369-4216G>T		intron_variant				ENSP00000494284.1
GATA3-AS1	ENST00000355358.1	n.1593C>A		non_coding_transcript_exon_variant	2/2	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

GnomAD3 exomes AF: 0.867 AC: 207232 AN: 239144 Hom.: 90247 AF XY: 0.866 AC XY: 113349 AN XY: 130900

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 SAS exome AF: 0.930

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

Gnomad4 AFR exome AF: 0.920

Gnomad4 AMR exome AF: 0.919

Gnomad4 ASJ exome AF: 0.858

Gnomad4 EAS exome AF: 0.990

Gnomad4 SAS exome AF: 0.931

Gnomad4 FIN exome AF: 0.821

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.846

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

Gnomad4 AFR AF: 0.915

Gnomad4 AMR AF: 0.879

Gnomad4 ASJ AF: 0.866

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.941

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.863

Alfa AF: 0.828 Hom.: 111926

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs501764; hg19: chr10-8093034;