X-48791321-A-G

Variant summary

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

The NM_002049.4(GATA1):c.212A>G(p.His71Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000096 in 1,197,474 control chromosomes in the GnomAD database, including 1 homozygotes. There are 39 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H71P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.00010 ( 1 hom. 39 hem. )

Consequence

GATA1
NM_002049.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.98

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=0.01828307).

BP6

Variant X-48791321-A-G is Benign according to our data. Variant chrX-48791321-A-G is described in ClinVar as [Benign]. Clinvar id is 533696.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000449 (5/111467) while in subpopulation EAS AF= 0.00141 (5/3539). AF 95% confidence interval is 0.000556. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome at 20 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA1	NM_002049.4 linkuse as main transcript	c.212A>G	p.His71Arg	missense_variant	2/6	ENST00000376670.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA1	ENST00000376670.9 linkuse as main transcript	c.212A>G	p.His71Arg	missense_variant	2/6	1	NM_002049.4	P4	P15976-1

Frequencies

GnomAD3 genomes

AF:

0.0000449

AC:

AN:

111415

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33717

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00141

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000319

AC:

AN:

160056

Hom.:

AF XY:

0.000396

AC XY:

AN XY:

50544

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00401

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

110

AN:

1086007

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

353769

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00321

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000239

Gnomad4 OTH exome

AF:

0.000263

GnomAD4 genome

AF:

0.0000449

AC:

AN:

111467

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33779

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00141

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000151

ExAC

AF:

0.000315

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.010

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Pathogenic

0.80

D;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.018

T;T

MetaSVM

Pathogenic

0.85

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.13

T;T

Polyphen

0.31

B;.

Vest4

0.49

MutPred

0.47

Gain of phosphorylation at S72 (P = 0.0966);Gain of phosphorylation at S72 (P = 0.0966);

MVP

0.86

MPC

0.28

ClinPred

0.23

GERP RS

3.3

Varity_R

0.44

gMVP

0.68

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