dbSNP rs554517990: GATA3:c.-48G>T (chr10-8055608-G-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001002295.2(GATA3):c.-48G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000549 in 1,521,422 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

GATA3
NM_001002295.2 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.696

Publications

1 publications found

Variant links:

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 links:

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

GATA3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 10-8055608-G-T is Benign according to our data. Variant chr10-8055608-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 301116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00308 (454/147362) while in subpopulation AFR AF = 0.0107 (423/39450). AF 95% confidence interval is 0.00988. There are 1 homozygotes in GnomAd4. There are 208 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 454 AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA3	NM_001002295.2	MANE Select	c.-48G>T	5_prime_UTR	Exon 2 of 6	NP_001002295.1	P23771-2
GATA3	NM_001441115.1		c.-48G>T	5_prime_UTR	Exon 2 of 6	NP_001428044.1
GATA3	NM_001441116.1		c.-48G>T	5_prime_UTR	Exon 3 of 7	NP_001428045.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA3	ENST00000379328.9	TSL:1 MANE Select	c.-48G>T	5_prime_UTR	Exon 2 of 6	ENSP00000368632.3	P23771-2
GATA3	ENST00000346208.4	TSL:1	c.-48G>T	5_prime_UTR	Exon 2 of 6	ENSP00000341619.3	P23771-1
GATA3	ENST00000872595.1		c.-48G>T	5_prime_UTR	Exon 3 of 7	ENSP00000542654.1

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

451

AN:

147274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00174

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00149

GnomAD2 exomes

AF:

0.000675

AC:

AN:

128930

AF XY:

0.000507

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.000255

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.000515

GnomAD4 exome

AF:

0.000278

AC:

382

AN:

1374060

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

156

AN XY:

677672

show subpopulations

African (AFR)

AF:

0.0105

AC:

323

AN:

30792

American (AMR)

AF:

0.000434

AC:

AN:

34568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24596

East Asian (EAS)

AF:

0.00

AC:

AN:

34628

South Asian (SAS)

AF:

0.00

AC:

AN:

77300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38450

Middle Eastern (MID)

AF:

0.000659

AC:

AN:

4550

European-Non Finnish (NFE)

AF:

0.00000839

AC:

AN:

1072116

Other (OTH)

AF:

0.000561

AC:

AN:

57060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00308

AC:

454

AN:

147362

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

208

AN XY:

71896

show subpopulations

African (AFR)

AF:

0.0107

AC:

423

AN:

39450

American (AMR)

AF:

0.00173

AC:

AN:

14994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3416

East Asian (EAS)

AF:

0.00

AC:

AN:

4962

South Asian (SAS)

AF:

0.00

AC:

AN:

4608

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9998

Middle Eastern (MID)

AF:

0.00355

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66724

Other (OTH)

AF:

0.00147

AC:

AN:

2036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000697

Hom.:

Bravo

AF:

0.00334

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hypoparathyroidism, deafness, renal disease syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.70

Mutation Taster

=300/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over