rs4902311
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001355436.2(SPTB):c.4752C>T(p.Asn1584=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 1,613,800 control chromosomes in the GnomAD database, including 4,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.057 ( 296 hom., cov: 32)
Exomes 𝑓: 0.073 ( 4302 hom. )
Consequence
SPTB
NM_001355436.2 synonymous
NM_001355436.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.672
Genes affected
SPTB (HGNC:11274): (spectrin beta, erythrocytic) This locus encodes a member of the spectrin gene family. Spectrin proteins, along with ankyrin, play a role in cell membrane organization and stability. The protein encoded by this locus functions in stability of erythrocyte membranes, and mutations in this gene have been associated with spherocytosis type 2, hereditary elliptocytosis, and neonatal hemolytic anemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 14-64775215-G-A is Benign according to our data. Variant chr14-64775215-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 257125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64775215-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.672 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTB | NM_001355436.2 | c.4752C>T | p.Asn1584= | synonymous_variant | 23/36 | ENST00000644917.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTB | ENST00000644917.1 | c.4752C>T | p.Asn1584= | synonymous_variant | 23/36 | NM_001355436.2 | P1 | ||
SPTB | ENST00000553938.5 | c.747C>T | p.Asn249= | synonymous_variant | 4/18 | 1 | |||
SPTB | ENST00000389722.7 | c.4752C>T | p.Asn1584= | synonymous_variant | 22/35 | 2 | P1 | ||
SPTB | ENST00000389720.4 | c.4752C>T | p.Asn1584= | synonymous_variant | 23/32 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0573 AC: 8725AN: 152184Hom.: 296 Cov.: 32
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GnomAD3 exomes AF: 0.0603 AC: 15135AN: 251122Hom.: 586 AF XY: 0.0607 AC XY: 8249AN XY: 135834
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GnomAD4 exome AF: 0.0730 AC: 106737AN: 1461498Hom.: 4302 Cov.: 33 AF XY: 0.0722 AC XY: 52475AN XY: 727074
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GnomAD4 genome ? AF: 0.0573 AC: 8730AN: 152302Hom.: 296 Cov.: 32 AF XY: 0.0572 AC XY: 4263AN XY: 74464
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 27, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Elliptocytosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Spherocytosis, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at