rs63750840
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_000518.5(HBB):c.60C>T(p.Asn20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
HBB
NM_000518.5 synonymous
NM_000518.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.90
Genes affected
HBB (HGNC:4827): (hemoglobin subunit beta) The alpha (HBA) and beta (HBB) loci determine the structure of the 2 types of polypeptide chains in adult hemoglobin, Hb A. The normal adult hemoglobin tetramer consists of two alpha chains and two beta chains. Mutant beta globin causes sickle cell anemia. Absence of beta chain causes beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia. 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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 11-5226962-G-A is Benign according to our data. Variant chr11-5226962-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1083541.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}. Variant chr11-5226962-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-3.9 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HBB | NM_000518.5 | c.60C>T | p.Asn20= | synonymous_variant | 1/3 | ENST00000335295.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HBB | ENST00000335295.4 | c.60C>T | p.Asn20= | synonymous_variant | 1/3 | 1 | NM_000518.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
3
AN:
152118
Hom.:
Cov.:
32
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:
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251238Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135776
GnomAD3 exomes
AF:
AC:
2
AN:
251238
Hom.:
AF XY:
AC XY:
1
AN XY:
135776
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461548Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727110
GnomAD4 exome
AF:
AC:
16
AN:
1461548
Hom.:
Cov.:
33
AF XY:
AC XY:
4
AN XY:
727110
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
GnomAD4 genome
?
AF:
AC:
3
AN:
152118
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74328
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 25, 2023 | To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00002 (3/152118 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on HBB mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites . Based on the available information, we are unable to determine the clinical significance of this variant. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 30, 2023 | - - |
beta Thalassemia Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 24, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 6
Find out detailed SpliceAI scores and Pangolin per-transcript scores at