Genetic Variant GATA1:c.-19-5C>T (chrX-48791086-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002049.4(GATA1):c.-19-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000076 in 1,053,106 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000076 ( 0 hom. 4 hem. )

Consequence

GATA1
NM_002049.4 splice_region, intron

Scores

Splicing: ADA: 0.0002267

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0490

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

GATA1-Related X-Linked Cytopenia
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
thrombocytopenia, X-linked, with or without dyserythropoietic anemia
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
beta-thalassemia-X-linked thrombocytopenia syndrome
Inheritance: XL Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
Diamond-Blackfan anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cutaneous porphyria
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
thrombocytopenia with congenital dyserythropoietic anemia
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked dyserythropoetic anemia with abnormal platelets and neutropenia
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

GATA1 links:

ENSG00000232828 (HGNC:):

ENSG00000232828 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant X-48791086-C-T is Benign according to our data. Variant chrX-48791086-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 258540.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 4 AR,XL,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002049.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA1	NM_002049.4	MANE Select	c.-19-5C>T		splice_region intron	N/A	NP_002040.1	P15976-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA1	ENST00000376670.9	TSL:1 MANE Select	c.-19-5C>T	splice_region intron	N/A	ENSP00000365858.3	P15976-1
GATA1	ENST00000696450.1		c.-19-5C>T	splice_region intron	N/A	ENSP00000512637.1	A0A8Q3SIN3
GATA1	ENST00000696452.1		c.-29-758C>T	intron	N/A	ENSP00000512639.1	A0A8Q3SIT6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000262

AC:

AN:

152798

AF XY:

0.0000419

show subpopulations

Gnomad AFR exome

AF:

0.0000917

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000161

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000158

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000760

AC:

AN:

1053106

Hom.:

Cov.:

AF XY:

0.0000122

AC XY:

AN XY:

328876

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25555

American (AMR)

AF:

0.00

AC:

AN:

33649

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18783

East Asian (EAS)

AF:

0.0000336

AC:

AN:

29777

South Asian (SAS)

AF:

0.0000194

AC:

AN:

51466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3967

European-Non Finnish (NFE)

AF:

0.00000745

AC:

AN:

805617

Other (OTH)

AF:

0.00

AC:

AN:

44566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.4

(source)

DANN

Benign

0.67

PhyloP100

0.049

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00023

dbscSNV1_RF

Benign

0.0020

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over