rs150572851

Positions:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002049.4(GATA1):c.163G>A(p.Ala55Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,205,296 control chromosomes in the GnomAD database, including 2 homozygotes. There are 121 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00022 ( 2 hom. 115 hem. )

Consequence

GATA1
NM_002049.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:4O:1

Conservation

PhyloP100: 0.638

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012266785).

BP6

Variant X-48791272-G-A is Benign according to our data. Variant chrX-48791272-G-A is described in ClinVar as [Benign]. Clinvar id is 134462.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-48791272-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000178 (20/112047) while in subpopulation SAS AF= 0.000742 (2/2697). AF 95% confidence interval is 0.000131. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA1	NM_002049.4 linkuse as main transcript	c.163G>A	p.Ala55Thr	missense_variant	2/6	ENST00000376670.9	NP_002040.1	P15976-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA1	ENST00000376670.9 linkuse as main transcript	c.163G>A	p.Ala55Thr	missense_variant	2/6	1	NM_002049.4	ENSP00000365858.3		P15976-1

Frequencies

GnomAD3 genomes

AF:

0.000179

AC:

AN:

111992

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

34174

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000740

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.000226

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000320

AC:

AN:

168913

Hom.:

AF XY:

0.000498

AC XY:

AN XY:

56271

show subpopulations

Gnomad AFR exome

AF:

0.0000838

Gnomad AMR exome

AF:

0.0000381

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00220

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000175

Gnomad OTH exome

AF:

0.000236

GnomAD4 exome

AF:

0.000220

AC:

240

AN:

1093249

Hom.:

Cov.:

AF XY:

0.000320

AC XY:

115

AN XY:

359425

show subpopulations

Gnomad4 AFR exome

AF:

0.0000759

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00264

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000905

Gnomad4 OTH exome

AF:

0.000283

GnomAD4 genome

AF:

0.000178

AC:

AN:

112047

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

34239

show subpopulations

Gnomad4 AFR

AF:

0.000162

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000742

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000226

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000242

Hom.:

Bravo

AF:

0.000170

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000447

AC:

ExAC

AF:

0.000305

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

GATA1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 14, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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 22, 2024

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

T;T

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.61

T;T

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.012

T;T

MetaSVM

Uncertain

0.17

MutationAssessor

Benign

0.55

N;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.25

Sift

Benign

0.45

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.99

D;.

Vest4

0.27

MVP

0.76

MPC

0.29

ClinPred

0.014

GERP RS

1.4

Varity_R

0.056

gMVP

0.33

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