rs139614533

chrX-48791283-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.54

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 11 XL gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 45 AN: 112089 Hom.: 0 Cov.: 23 AF XY: 0.000321 AC XY: 11 AN XY: 34261

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: 70 AN: 168554 Hom.: 0 AF XY: 0.000304 AC XY: 17 AN XY: 55916

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.: 0 Cov.: 32 AF XY: 0.000145 AC XY: 52 AN XY: 359275

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: 45 AN: 112143 Hom.: 0 Cov.: 23 AF XY: 0.000320 AC XY: 11 AN XY: 34325

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.: 2

Bravo AF: 0.000298

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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	-	- -

Complete trisomy 21 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

Invitae

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

Other links and lift over

dbSNP: rs139614533; hg19: chrX-48649690; COSMIC: COSV64962588;