rs61735969

chrX-48794095-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.1173G>A(p.Thr391=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000475 in 1,197,294 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 140 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 0.0023 (0 hom., 70 hem., cov: 23)
  • Exomes 𝑓: 0.00028 (0 hom. 70 hem.)
• Consequence: GATA1 NM_002049.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.116

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=-0.81).
• BP6: Variant X-48794095-G-A is Benign according to our data. Variant chrX-48794095-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.116 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00235 (263/112008) while in subpopulation AFR AF= 0.00819 (253/30889). AF 95% confidence interval is 0.00736. There are 0 homozygotes in gnomad4. There are 70 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 70 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA1	NM_002049.4	c.1173G>A	p.Thr391=	synonymous_variant	6/6	ENST00000376670.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA1	ENST00000376670.9	c.1173G>A	p.Thr391=	synonymous_variant	6/6	1	NM_002049.4	P4

Frequencies

GnomAD3 genomes AF: 0.00235 AC: 263 AN: 111954 Hom.: 0 Cov.: 23 AF XY: 0.00205 AC XY: 70 AN XY: 34158

Gnomad AFR AF: 0.00821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00132

GnomAD3 exomes AF: 0.000726 AC: 120 AN: 165237 Hom.: 0 AF XY: 0.000518 AC XY: 28 AN XY: 54025

Gnomad AFR exome AF: 0.00892

Gnomad AMR exome AF: 0.000157

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000198

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000282 AC: 306 AN: 1085286 Hom.: 0 Cov.: 31 AF XY: 0.000198 AC XY: 70 AN XY: 352898

Gnomad4 AFR exome AF: 0.00965

Gnomad4 AMR exome AF: 0.000296

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000388

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000275

Gnomad4 OTH exome AF: 0.000395

GnomAD4 genome AF: 0.00235 AC: 263 AN: 112008 Hom.: 0 Cov.: 23 AF XY: 0.00205 AC XY: 70 AN XY: 34222

Gnomad4 AFR AF: 0.00819

Gnomad4 AMR AF: 0.000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000189

Gnomad4 OTH AF: 0.00130

Alfa AF: 0.00135 Hom.: 5

Bravo AF: 0.00280

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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	May 25, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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	-0.81
Cadd	Benign	1.4
Dann	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs61735969; hg19: chrX-48652502;