14-64774510-A-G
Variant names:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001355436.2(SPTB):c.4860T>C(p.Ile1620Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,553,578 control chromosomes in the GnomAD database, including 73,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.41 ( 16309 hom., cov: 32)
Exomes 𝑓: 0.27 ( 57595 hom. )
Consequence
SPTB
NM_001355436.2 synonymous
NM_001355436.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.24
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 14-64774510-A-G is Benign according to our data. Variant chr14-64774510-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 257128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64774510-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-1.24 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPTB | NM_001355436.2 | c.4860T>C | p.Ile1620Ile | synonymous_variant | Exon 24 of 36 | ENST00000644917.1 | NP_001342365.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPTB | ENST00000644917.1 | c.4860T>C | p.Ile1620Ile | synonymous_variant | Exon 24 of 36 | NM_001355436.2 | ENSP00000495909.1 | |||
SPTB | ENST00000553938.5 | c.855T>C | p.Ile285Ile | synonymous_variant | Exon 5 of 18 | 1 | ENSP00000451324.1 | |||
SPTB | ENST00000389722.7 | c.4860T>C | p.Ile1620Ile | synonymous_variant | Exon 23 of 35 | 2 | ENSP00000374372.3 | |||
SPTB | ENST00000389720.4 | c.4860T>C | p.Ile1620Ile | synonymous_variant | Exon 24 of 32 | 5 | ENSP00000374370.4 |
Frequencies
GnomAD3 genomes AF: 0.410 AC: 62253AN: 151850Hom.: 16267 Cov.: 32
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GnomAD3 exomes AF: 0.324 AC: 51720AN: 159502Hom.: 9738 AF XY: 0.315 AC XY: 26565AN XY: 84290
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GnomAD4 exome AF: 0.270 AC: 378130AN: 1401610Hom.: 57595 Cov.: 35 AF XY: 0.269 AC XY: 186176AN XY: 691638
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GnomAD4 genome AF: 0.410 AC: 62356AN: 151968Hom.: 16309 Cov.: 32 AF XY: 0.412 AC XY: 30624AN XY: 74286
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Nov 28, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Dec 22, 2021
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
not specified Benign:1
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PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Elliptocytosis Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Spherocytosis, Dominant Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Hereditary spherocytosis type 2 Benign:1
Jul 15, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
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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