Variant rs139614533 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002049.4(GATA1):c.174G>A(p.Ala58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,205,216 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 63 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 11 hem., cov: 23)

Exomes 𝑓: 0.00015 ( 0 hom. 52 hem. )

Consequence

GATA1
NM_002049.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.54

Variant links:

Genes affected

GATA1 (HGNC:4170): (GATA binding protein 1) This gene encodes a protein which belongs to the GATA family of transcription factors. The protein plays an important role in erythroid development by regulating the switch of fetal hemoglobin to adult hemoglobin. Mutations in this gene have been associated with X-linked dyserythropoietic anemia and thrombocytopenia. [provided by RefSeq, Jul 2008]

GATA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.05).

BP6

Variant X-48791283-G-A is Benign according to our data. Variant chrX-48791283-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.54 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000401 (45/112143) while in subpopulation EAS AF= 0.00705 (25/3545). AF 95% confidence interval is 0.0049. There are 0 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA1	NM_002049.4 linkuse as main transcript	c.174G>A	p.Ala58=	synonymous_variant	2/6	ENST00000376670.9	NP_002040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA1	ENST00000376670.9 linkuse as main transcript	c.174G>A	p.Ala58=	synonymous_variant	2/6	1	NM_002049.4	ENSP00000365858	P4	P15976-1

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

112089

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

AN XY:

34261

show subpopulations

Gnomad AFR

AF:

0.000422

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00703

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.000657

GnomAD3 exomes

AF:

0.000415

AC:

AN:

168554

Hom.:

AF XY:

0.000304

AC XY:

AN XY:

55916

show subpopulations

Gnomad AFR exome

AF:

0.000586

Gnomad AMR exome

AF:

0.0000381

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00363

Gnomad SAS exome

AF:

0.000407

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000540

Gnomad OTH exome

AF:

0.000712

GnomAD4 exome

AF:

0.000151

AC:

165

AN:

1093073

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

359275

show subpopulations

Gnomad4 AFR exome

AF:

0.000304

Gnomad4 AMR exome

AF:

0.0000866

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00296

Gnomad4 SAS exome

AF:

0.000434

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000191

Gnomad4 OTH exome

AF:

0.000566

GnomAD4 genome

AF:

0.000401

AC:

AN:

112143

Hom.:

Cov.:

AF XY:

0.000320

AC XY:

AN XY:

34325

show subpopulations

Gnomad4 AFR

AF:

0.000421

Gnomad4 AMR

AF:

0.000281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00705

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.000648

Alfa

AF:

0.000391

Hom.:

Bravo

AF:

0.000298

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 08, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Down syndrome;C1839161:Beta-thalassemia-X-linked thrombocytopenia syndrome;C3550789:Thrombocytopenia, X-linked, with or without dyserythropoietic anemia;C3550856:X-linked dyserythropoetic anemia with abnormal platelets and neutropenia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 27, 2021

- -

Diamond-Blackfan anemia;C1845837:GATA binding protein 1 related thrombocytopenia with dyserythropoiesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.39

DANN

Benign

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over