chr14-64775349-T-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001355436.2(SPTB):āc.4618A>Cā(p.Arg1540=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,613,402 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0032 ( 3 hom., cov: 33)
Exomes š: 0.0049 ( 30 hom. )
Consequence
SPTB
NM_001355436.2 synonymous
NM_001355436.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.04
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=-0.64).
BP6
Variant 14-64775349-T-G is Benign according to our data. Variant chr14-64775349-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 257122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64775349-T-G is described in Lovd as [Benign]. Variant chr14-64775349-T-G is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.04 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00494 (7212/1461078) while in subpopulation NFE AF= 0.00591 (6575/1111658). AF 95% confidence interval is 0.00579. There are 30 homozygotes in gnomad4_exome. There are 3516 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPTB | NM_001355436.2 | c.4618A>C | p.Arg1540= | synonymous_variant | 23/36 | ENST00000644917.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPTB | ENST00000644917.1 | c.4618A>C | p.Arg1540= | synonymous_variant | 23/36 | NM_001355436.2 | P1 | ||
SPTB | ENST00000553938.5 | c.613A>C | p.Arg205= | synonymous_variant | 4/18 | 1 | |||
SPTB | ENST00000389722.7 | c.4618A>C | p.Arg1540= | synonymous_variant | 22/35 | 2 | P1 | ||
SPTB | ENST00000389720.4 | c.4618A>C | p.Arg1540= | synonymous_variant | 23/32 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00317 AC: 482AN: 152206Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00308 AC: 768AN: 249650Hom.: 0 AF XY: 0.00323 AC XY: 437AN XY: 135132
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GnomAD4 exome AF: 0.00494 AC: 7212AN: 1461078Hom.: 30 Cov.: 35 AF XY: 0.00484 AC XY: 3516AN XY: 726788
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GnomAD4 genome AF: 0.00316 AC: 482AN: 152324Hom.: 3 Cov.: 33 AF XY: 0.00313 AC XY: 233AN XY: 74484
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 09, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | SPTB: BP4, BP7, BS2 - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
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