11-5249466-C-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_000559.3(HBG1):c.217G>C(p.Gly73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as other (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.
Frequency
Genomes: not found (cov: 9)
Exomes 𝑓: 0.0000037 ( 0 hom. )
Consequence
HBG1
NM_000559.3 missense
NM_000559.3 missense
Scores
3
7
7
Clinical Significance
Conservation
PhyloP100: 1.47
Publications
2 publications found
Genes affected
HBG1 (HGNC:4831): (hemoglobin subunit gamma 1) The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'-epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]
HBG1 Gene-Disease associations (from GenCC):
- hereditary persistence of fetal hemoglobin-beta-thalassemia syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- delta-beta-thalassemiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- hereditary persistence of fetal hemoglobin-sickle cell disease syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
9
GnomAD4 exome AF: 0.00000373 AC: 3AN: 804484Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0AN XY: 407426 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
804484
Hom.:
Cov.:
15
AF XY:
AC XY:
0
AN XY:
407426
show subpopulations
African (AFR)
AF:
AC:
0
AN:
18458
American (AMR)
AF:
AC:
0
AN:
32908
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18584
East Asian (EAS)
AF:
AC:
3
AN:
31340
South Asian (SAS)
AF:
AC:
0
AN:
57566
European-Finnish (FIN)
AF:
AC:
0
AN:
39832
Middle Eastern (MID)
AF:
AC:
0
AN:
2962
European-Non Finnish (NFE)
AF:
AC:
0
AN:
566412
Other (OTH)
AF:
AC:
0
AN:
36422
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
9
ClinVar
Significance: other
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
HEMOGLOBIN F (IWATA) Other:1
Jul 15, 2011
OMIM
Significance:other
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
PhyloP100
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0106);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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