11-5248439-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP3BP6_Moderate
The NM_000559.3(HBG1):c.364G>A(p.Glu122Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
HBG1
NM_000559.3 missense
NM_000559.3 missense
Scores
2
8
7
Clinical Significance
Conservation
PhyloP100: 3.03
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: Likely_benign. The variant received -1 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.772
BP6
Variant 11-5248439-C-T is Benign according to our data. Variant chr11-5248439-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 15023.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152088Hom.: 0 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
8
AN:
152088
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000358 AC: 9AN: 251182 AF XY: 0.0000442 show subpopulations
GnomAD2 exomes
AF:
AC:
9
AN:
251182
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461782Hom.: 0 Cov.: 34 AF XY: 0.0000316 AC XY: 23AN XY: 727196 show subpopulations
GnomAD4 exome
AF:
AC:
65
AN:
1461782
Hom.:
Cov.:
34
AF XY:
AC XY:
23
AN XY:
727196
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
64
AN:
1111920
Other (OTH)
AF:
AC:
1
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.496
Heterozygous variant carriers
0
4
7
11
14
18
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152088Hom.: 0 Cov.: 30 AF XY: 0.0000673 AC XY: 5AN XY: 74300 show subpopulations
GnomAD4 genome
AF:
AC:
8
AN:
152088
Hom.:
Cov.:
30
AF XY:
AC XY:
5
AN XY:
74300
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41362
American (AMR)
AF:
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
7
AN:
68042
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.438
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ExAC
AF:
AC:
5
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1Other:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Fetal hemoglobin quantitative trait locus 1 Benign:1
Oct 21, 2021
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
HEMOGLOBIN F (HULL) Other:1
Jul 15, 2011
OMIM
Significance:other
Review Status:no assertion criteria provided
Collection Method:literature only
- -
HEMOGLOBIN F (SIENA) 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
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
PhyloP100
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;.
REVEL
Pathogenic
Sift
Uncertain
D;.;.
Sift4G
Benign
T;.;.
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
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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