rs3824662

Variant names:

• chr10-8062245-C-A
• rs3824662
• NM_001002295.2:c.779-1748C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-8062245-C-A
• chr10-8062245-C-G
• chr10-8062245-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001002295.2(GATA3):​c.779-1748C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,898 control chromosomes in the GnomAD database, including 2,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.18 (2831 hom., cov: 32)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05
• Publications: 89 publications found

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]

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-8062245-C-A is Benign according to our data. Variant chr10-8062245-C-A is described in ClinVar as Benign. ClinVar VariationId is 1223371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002295.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	NM_001002295.2	MANE Select	c.779-1748C>A		intron	N/A	NP_001002295.1
	GATA3	NM_001441115.1		c.779-1748C>A		intron	N/A	NP_001428044.1
	GATA3	NM_001441116.1		c.779-1748C>A		intron	N/A	NP_001428045.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.779-1748C>A		intron	N/A	ENSP00000368632.3
	GATA3	ENST00000346208.4	TSL:1	c.779-1751C>A		intron	N/A	ENSP00000341619.3
	GATA3	ENST00000461472.1	TSL:3	c.442+3404C>A		intron	N/A	ENSP00000515407.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27039 AN: 151782 Hom.: 2825 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.178 AC: 27042 AN: 151898 Hom.: 2831 Cov.: 32 AF XY: 0.185 AC XY: 13719 AN XY: 74196

African (AFR) AF: 0.0990 AC: 4103 AN: 41438

American (AMR) AF: 0.294 AC: 4484 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3472

East Asian (EAS) AF: 0.295 AC: 1523 AN: 5166

South Asian (SAS) AF: 0.197 AC: 949 AN: 4814

European-Finnish (FIN) AF: 0.242 AC: 2529 AN: 10462

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11880 AN: 67952

Other (OTH) AF: 0.199 AC: 420 AN: 2112

Alfa AF: 0.180 Hom.: 9249

Bravo AF: 0.185

Asia WGS AF: 0.206 AC: 712 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	B-cell childhood acute lymphoblastic leukemia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.54
DANN	Benign	0.50
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3824662; hg19: chr10-8104208;