X-48791174-C-G

Variant summary

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

The NM_002049.4(GATA1):c.65C>G(p.Ala22Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,206,198 control chromosomes in the GnomAD database, including 2 homozygotes. There are 211 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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. A22T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., 41 hem., cov: 22)

Exomes 𝑓: 0.00043 ( 2 hom. 170 hem. )

Consequence

GATA1
NM_002049.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00900

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=0.0058964193).

BP6

Variant X-48791174-C-G is Benign according to our data. Variant chrX-48791174-C-G is described in ClinVar as [Benign]. Clinvar id is 1951191.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000651 (73/112084) while in subpopulation NFE AF= 0.000358 (19/53026). AF 95% confidence interval is 0.000234. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd at 41 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA1	NM_002049.4 linkuse as main transcript	c.65C>G	p.Ala22Gly	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.65C>G	p.Ala22Gly	missense_variant	2/6	1	NM_002049.4	P4	P15976-1

Frequencies

GnomAD3 genomes

AF:

0.000651

AC:

AN:

112084

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

34240

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00862

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000358

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000814

AC:

141

AN:

173201

Hom.:

AF XY:

0.000927

AC XY:

AN XY:

59345

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00790

Gnomad NFE exome

AF:

0.000197

Gnomad OTH exome

AF:

0.00139

GnomAD4 exome

AF:

0.000433

AC:

474

AN:

1094114

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

170

AN XY:

360000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00995

Gnomad4 NFE exome

AF:

0.0000667

Gnomad4 OTH exome

AF:

0.000370

GnomAD4 genome

AF:

0.000651

AC:

AN:

112084

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

34240

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00862

Gnomad4 NFE

AF:

0.000358

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000381

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000759

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

Nov 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.24

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.27

T;T

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.66

T;T

MetaRNN

Benign

0.0059

T;T

MetaSVM

Uncertain

0.57

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

0.80

N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.21

N;N

REVEL

Benign

0.27

Sift

Benign

0.21

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.54

P;.

Vest4

0.21

MVP

0.67

MPC

0.050

ClinPred

0.031

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.087

gMVP

0.17

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